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Experimentally_validated_variants.tsv
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Experimentally_validated_variants.tsv
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Genomic_Variant Chr Position Ref Alt Gene NCBI_Gene_ID Gene_ID_Link Gene_Location Variant_Type Variant_Annotation Protein Protein_Length NCBI_Protein_ID Protein_ID_Link Amino_Acid_Change VoCs_and_VoIs VoCs_and_VoIs_link VoCs_and_VoIs_Description SIFT_Score SIFT_Prediction GERP PhyloP PhastCons Uniprot_Domains UNIPROT_Disulphite_Bond UNIPROT_glyphos UNIPROT_Transmembrane IEDB_B-Cell_Epitopes IEDB_CD4_Epitopes IEDB_cd4Epitope_Score IEDB_CD8_Epitopes IEDB_cd8Epitope_Score MPDI_Potential_Immunogenic_Regions MPDI_Potential_Immunodominant_Epitopes ARTIC_Primers RT-PCR_Primers/Probes Sequencing_Error_Sites Homoplasic_Positions Hypermutable_Sites Variant_Category Co_Mutations Global_Allele_Frequency Method_of_Study Experiment Functional_Consequence Reference Reference_Link Article Authors Allele_Frequency_by_Geography Location_link IndiCoV_Link
23066G>A 1 23066 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 G502S None - None 0.26 Tolerated -2.71 -0.488315 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000003071300909 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in G502 residue might potentially alter viral binding properties. Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012https://doi.org/10.3390/vaccines8030355# https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Asia(0.00000337090771803031),Europe(0.00000364218082456546),NorthAmerica(0.00000249390862817568)
23066G>A 1 23066 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 G502S None - None 0.26 Tolerated -2.71 -0.488315 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000003071300909 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in G502 residue might potentially alter viral binding properties. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://pubmed.ncbi.nlm.nih.gov/32635180/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Asia(0.00000337090771803031),Europe(0.00000364218082456546),NorthAmerica(0.00000249390862817568) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a9c&&LOCATION=1:23066:G:A
22907T>G 1 22907 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y449D None - None 0.08 Tolerated NA -9.60239 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000007239494999 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; Study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y449 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012https://doi.org/10.3390/vaccines8030355# https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Africa(0.0000399656295585796),Europe(0.0000109265424736964),NorthAmerica(0.00000249390862817568)
22907T>G 1 22907 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y449D None - None 0.08 Tolerated NA -9.60239 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000007239494999 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; Study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y449 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://pubmed.ncbi.nlm.nih.gov/32635180/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Africa(0.0000399656295585796),Europe(0.0000109265424736964),NorthAmerica(0.00000249390862817568) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858bb&&LOCATION=1:22907:T:G
22907T>C 1 22907 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y449H None - None 0.32 Tolerated NA -9.60239 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0001708959577 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; Study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y449 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012https://doi.org/10.3390/vaccines8030355# https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Africa(0.00497572088004316),Asia(0.0000910145083868184),Europe(0.000177657486887137),NorthAmerica(0.0000305503806951521),Oceania(0.000191067590160019),SouthAmerica(0.000073835768155688)
22907T>C 1 22907 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y449H None - None 0.32 Tolerated NA -9.60239 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0001708959577 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; Study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y449 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://pubmed.ncbi.nlm.nih.gov/32635180/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Africa(0.00497572088004316),Asia(0.0000910145083868184),Europe(0.000177657486887137),NorthAmerica(0.0000305503806951521),Oceania(0.000191067590160019),SouthAmerica(0.000073835768155688) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858ba&&LOCATION=1:22907:T:C
22909T>G 1 22909 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Stop Gain Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y449X None - None NA NA -3.3 -8.22904 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; Study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y449is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012https://doi.org/10.3390/vaccines8030355# https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding 0
22909T>G 1 22909 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Stop Gain Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y449X None - None NA NA -3.3 -8.22904 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; Study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y449is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://pubmed.ncbi.nlm.nih.gov/32635180/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858c0&&LOCATION=1:22909:T:G
23075T>G 1 23075 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505D None - None 0.2 Tolerated -2.08 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000000658135909 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y505 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ , https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Asia(0.00000337090771803031),Europe(0.000000404686758285051),NorthAmerica(0.00000062347715704392) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85ab8&&LOCATION=1:23075:T:G
23076A>T 1 23076 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505F None - None 0.66 Tolerated 0.461 0.885039 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000003510058181 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y505 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ , https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Africa(0.0000399656295585796),Europe(0.00000202343379142525),NorthAmerica(0.00000561129441339528) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85abb&&LOCATION=1:23076:A:T
23076A>C 1 23076 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505S None - None 0.38 Tolerated 0.461 0.885039 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000001096893182 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y505 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ , https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Africa(0.0000199828147792898),Europe(0.0000016187470331402) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85aba&&LOCATION=1:23076:A:C
23077C>A 1 23077 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Stop Gain Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505X None - None NA NA -3.3 -1.98652 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_QPYRVVVLSFELLHA 14 Surface glycoprotein_QPYRVVVL -1 NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y505 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ , https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85abc&&LOCATION=1:23077:C:A
23077C>G 1 23077 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Stop Gain Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505X None - None NA NA -3.3 -1.98652 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_QPYRVVVLSFELLHA 14 Surface glycoprotein_QPYRVVVL -1 NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis , Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking and Computational Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein ; This study includes RBD cloning, where The Spike receptor binding domain (RBD) from SARS-CoV-2 and additional sarbecovirus homologs were ordered as yeast codon-optimized gBlocks (IDT) and cloned into the pETcon yeast surface-display expression vector. This was followed by library mutagenesis, sequencing and variant phenotype calculation for ACE2-binding affinity. Y505 is one of the key residues contributing to the binding to the host receptor ACE2. Antibodies binding to these regions may block the virus binding to the host cell receptor ; Mutations to polar amino acids enhance expression at interface residues Y449, L455, F486, and Y505 consistent with the destabilizing effect of surface-exposed hydrophobic patches but these hydrophobic residues form ACE2-packing contacts and are required for binding. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ , https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85abd&&LOCATION=1:23077:C:G
24197G>T 1 24197 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A879S None - None 0.66 Tolerated 0.52 1.07924 0.590551 NA NA NA NA Surface glycoprotein_DEMIAQYTSALLAG NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.001575138609 Computational Analysis and Experimental Sequence alignments followed by Secondary structure predictions and protein dynamics study.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Effect of the mutations on the structural dynamics of Spike glycoprotein were measured using the differences of free energy (ΔΔG) between wild-type and mutant. The ΔΔG, as a consequence of mutation, correlates with the structural changes in three-dimensional structure of protein, and, thus, measures the effect of mutation on protein stability. A879S was predicted to destabilize the protein structure with the ΔΔG value of −0.384 kcal/mol.##Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera. These co-occurring mutations were found to have an decreased sensitivity to convalescent sera Chand, G. B., Banerjee, A., & Azad, G. K. (2020). Identification of twenty-five mutations in Surface glycoprotein (Spike) of SARS-CoV-2 among Indian isolates and their impact on protein dynamics. Gene Reports, 21, 100891. https://doi.org/10.1016/j.genrep.2020.100891 https://pubmed.ncbi.nlm.nih.gov/33015411/ Identification of twenty-five mutations in Surface glycoprotein (Spike) of SARS-CoV-2 among Indian isolates and their impact on protein dynamics##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Gyanendra Bahadur Chand , Atanu Banerjee , Gajendra Kumar Azad##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00239793777351478),Asia(0.00158769753519228),Europe(0.000963963858234991),NorthAmerica(0.00244091306982695),Oceania(0.000119417243850012),SouthAmerica(0.00302726649438321) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef867e5&&LOCATION=1:24197:G:T
24197G>T 1 24197 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A879S None - None 0.66 Tolerated 0.52 1.07924 0.590551 NA NA NA NA Surface glycoprotein_DEMIAQYTSALLAG NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.001575138609 Computational Analysis and Experimental Sequence alignments followed by Secondary structure predictions and protein dynamics study.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Effect of the mutations on the structural dynamics of Spike glycoprotein were measured using the differences of free energy (ΔΔG) between wild-type and mutant. The ΔΔG, as a consequence of mutation, correlates with the structural changes in three-dimensional structure of protein, and, thus, measures the effect of mutation on protein stability. A879S was predicted to destabilize the protein structure with the ΔΔG value of −0.384 kcal/mol.##Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera. These co-occurring mutations were found to have an decreased sensitivity to convalescent sera Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.00239793777351478),Asia(0.00158769753519228),Europe(0.000963963858234991),NorthAmerica(0.00244091306982695),Oceania(0.000119417243850012),SouthAmerica(0.00302726649438321)
22652G>T 1 22652 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D364Y None - None 0 Deleterious 1.65 4.256 0.551181 NA BetaCoV_S1-CTD NA NA Surface glycoprotein_KRISNCVADYSVLYNSASFST NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000001755029091 Computational Analysis and Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.####In-silico analysis on mutant affinity was also checked. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain.##D364Y displayed higher binding affinity to human ACE2, likely due to the enhanced structural stabilization of the RBD beta-sheet scaffold. Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Junxian Ou, Zhonghua Zhou, Ruixue Dai, Shan Zhao, Xiaowei Wu, Jing Zhang, Wendong Lan, Lilian Cui, Jianguo Wu, Donald Seto, James Chodosh, Gong Zhang, Qiwei Zhang Asia(0.0000101127231540909),Europe(0.00000121406027485515),NorthAmerica(0.00000124695431408784) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef855f9&&LOCATION=1:22652:G:T
22652G>T 1 22652 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D364Y None - None 0 Deleterious 1.65 4.256 0.551181 NA BetaCoV_S1-CTD NA NA Surface glycoprotein_KRISNCVADYSVLYNSASFST NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000001755029091 Computational Analysis and Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.####In-silico analysis on mutant affinity was also checked. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain.##D364Y displayed higher binding affinity to human ACE2, likely due to the enhanced structural stabilization of the RBD beta-sheet scaffold. Ou, J., Zhou, Z., Dai, R., Zhao, S., Wu, X., Zhang, J., Lan, W., Cui, L., Wu, J., Seto, D., Chodosh, J., Zhang, G., & Zhang, Q. (n.d.). Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity. https://doi.org/10.1101/2020.03.15.991844 https://www.biorxiv.org/content/10.1101/2020.03.15.991844v5.full Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity Asia(0.0000101127231540909),Europe(0.00000121406027485515),NorthAmerica(0.00000124695431408784)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Becerra-Flores, M., & Cardozo, T. (2020). SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate. International journal of clinical practice, 74(8), e13525. https://doi.org/10.1111/ijcp.13525 https://pubmed.ncbi.nlm.nih.gov/32374903/ SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Eaaswarkhanth, M., Al Madhoun, A., & Al-Mulla, F. (2020). Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality?. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 96, 459–460. https://doi.org/10.1016/j.ijid.2020.05.071 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247990/ Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality? Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., Hastie, K. M., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., Sheffield COVID-19 Genomics Group, McDanal, C., Perez, L. G., … Montefiori, D. C. (2020). Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell, 182(4), 812–827.e19. https://www.sciencedirect.com/science/article/pii/S0092867420308205 Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Maitra, A., Sarkar, M. C., Raheja, H., Biswas, N. K., Chakraborti, S., Singh, A. K., Ghosh, S., Sarkar, S., Patra, S., Mondal, R. K., Ghosh, T., Chatterjee, A., Banu, H., Majumdar, A., Chinnaswamy, S., Srinivasan, N., Dutta, S., & Das, S. (2020). Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility. Journal of Biosciences, 45(1), 1. https://doi.org/10.1007/s12038-020-00046-1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269891/ Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Raghav, S., Ghosh, A., Turuk, J., Kumar, S., Jha, A., Madhulika, S., Priyadarshini, M., Biswas, V. K., Sushree Shyamli, P., Singh, B., Singh, N., Singh, D., Datey, A., Kiran, A., Smita, S., Sabat, J., Bhattacharya, D., Dash, R., Senapati, S., … ILS COVID-19 team. (n.d.). SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein with TMPRSS2 depicted its enhanced interaction and virus infectivity. https://doi.org/10.1101/2020.07.23.217430 https://pubmed.ncbi.nlm.nih.gov/33329480/ SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein with TMPRSS2 depicted its enhanced interaction and virus infectivity Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Romano, C. M., Felix, A. C., Paula, A. V., Jesus, J. G., Andrade, P. S., Cândido, D., Oliveira, F. M., Ribeiro, A. C., Silva, F., Inemami, M., Costa, A. A., Leal, C., Figueiredo, W. M., Pannuti, C. S., Souza, W. M., Faria, N. R., & Sabino, E. C. (2021). SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo, 63, e36. https://doi.org/10.1590/S1678-9946202163036 https://pubmed.ncbi.nlm.nih.gov/33909850/#:~:text=1%20lineage%20was%20first%20identified,need%20for%20a%20global%20vigilance. SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Volz, E., Hill, V., McCrone, J. T., Price, A., Jorgensen, D., O'Toole, Á., Southgate, J., Johnson, R., Jackson, B., Nascimento, F. F., Rey, S. M., Nicholls, S. M., Colquhoun, R. M., da Silva Filipe, A., Shepherd, J., Pascall, D. J., Shah, R., Jesudason, N., Li, K., Jarrett, R., … Connor, T. R. (2021). Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell, 184(1), 64–75.e11. https://doi.org/10.1016/j.cell.2020.11.020 https://pubmed.ncbi.nlm.nih.gov/33275900/ Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Computational Analysis and Experimental Computational structural analysis using cryo electron microscopy structures of Spike protein followed by calculation of free energy changes due to mutations.##Maloney murine leukemia virus (MLV)-based pseudoviruses (PVs), expressing green fluorescent protein (GFP) and pseudotyped with the S protein of SARS-CoV-2 (SARS2) carrying the D614 or G614 genotype (SD614 and SG614, respectively) were produced from transfected HEK293T cells were used to determine the alteration properties of D614G mutation. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Zhang, L., Jackson, C. B., Mou, H., Ojha, A., Rangarajan, E. S., Izard, T., Farzan, M., & Choe, H. (2020). The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv : the preprint server for biology, 2020.06.12.148726.https://doi.org/10.1101/2020.06.12.148726 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310631/#:~:text=The%20S1%3AS2%20ratio%20is,protein%20incorporated%20into%20the%20virion. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity Lizhou Zhang, Cody B Jackson, Huihui Mou, Amrita Ojha, Erumbi S Rangarajan, Tina Izard, Michael Farzan, Hyeryun Choe##Manuel Becerra-Flores ,Timothy Cardozo##Sunil Raghav, Arup Ghosh, Jyotirmayee Turuk, Sugandh Kumar, Atimukta Jha, Swati Madhulika, Manasi Priyadarshini, Viplov K. Biswas, P. Sushree Shyamli, Bharati Singh, Neha Singh, Deepika Singh, Ankita Datey, Avula Kiran, Shuchi Smita, Jyotsnamayee Sabat, Debdutta Bhattacharya, Rupesh Dash, Shantibhushan Senapati, Tushar K. Beuria, Rajeeb Swain, Soma Chattopadhyay, Gulam Hussain Syed, Anshuman Dixit, Punit Prasad, Odisha COVID-19 study group, ILS COVID-19 team, Sanghamitra Pati, Ajay Parida##Bette Korber, Will M. Fischer, Sandrasegaram Gnanakaran, Celia C. LaBranche, Erica O. Saphire, David C. Montefiori##Muthukrishnan Eaaswarkhanth, Ashraf Al Madhoun, Fahd Al-Mulla##Arindam Maitra, Mamta Chawla Sarkar, Harsha Raheja,Nidhan K Biswas,Sohini Chakraborti,Animesh Kumar Singh,Shekhar Ghosh, Sumanta Sarkar,Subrata Patra,Rajiv Kumar Mondal, Trinath Ghosh,Ananya Chatterjee,Hasina Banu,Agniva Majumdar,Sreedhar Chinnaswamy,Narayanaswamy Srinivasan,Shanta Dutta, and Saumitra Das##Erik Volz 1, Verity Hill 2, John T McCrone 2, Anna Price 3, David Jorgensen 4, Áine O'Toole 2, Joel Southgate 5, Robert Johnson 4, Ben Jackson 2, Fabricia F Nascimento 4, Sara M Rey 6, Samuel M Nicholls 7, Rachel M Colquhoun 2, Ana da Silva Filipe 8, James Shepherd 8, David J Pascall 9, Rajiv Shah 8, Natasha Jesudason 8, Kathy Li 8, Ruth Jarrett 8, Nicole Pacchiarini 6, Matthew Bull 6, Lily Geidelberg 4, Igor Siveroni 4, COG-UK Consortium; Ian Goodfellow 10, Nicholas J Loman 7, Oliver G Pybus 11, David L Robertson 8, Emma C Thomson 8, Andrew Rambaut 12, Thomas R Connor 13##Author links open overlay panelMuthukumarRamanathana†Ian DFergusonb†WeiliMiaob†Paul AKhavarib##David Hodgson 1, Stefan Flasche 1, Mark Jit 1, Adam J Kucharski 1, CMMID COVID-19 Working Group; Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group##Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6#Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2##Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85e7d&&LOCATION=1:23403:A:G
22898G>A 1 22898 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 G446S None - None 0.82 Tolerated NA 0.385638 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.00008665456135 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking####Generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in G446 residue might potentially alter viral binding properties.#Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020a). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355# Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/32635180/#https://pubmed.ncbi.nlm.nih.gov/33112236/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design#Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.0000999140738964491),Asia(0.000158432662747425),Europe(0.0000781045443490148),NorthAmerica(0.0000872868019861488),Oceania(0.0000477668975400048),SouthAmerica(0.000084383735035072) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8589e&&LOCATION=1:22898:G:A
22899G>T 1 22899 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 G446V None - None 0.33 Tolerated NA 0.385638 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.001270421683 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.##Generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain#Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020a). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355# Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800# Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/32635180/#http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/#https://pubmed.ncbi.nlm.nih.gov/33112236/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design#The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity#Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang ; Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.000879243850288752),Asia(0.00132813764090394),Europe(0.00157058930890428),NorthAmerica(0.000871621065547401),Oceania(0.00050155242417005),SouthAmerica(0.000559042244607352) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858a5&&LOCATION=1:22899:G:T
22976A>G 1 22976 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 I472V None - None 1 Tolerated -1.71 2.63294 0.00787402 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_STEIYQAGSTPCNGV Surface glycoprotein_LKPFERDISTEIYQA 14 Surface glycoprotein_KPFERDISTEI -1 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.00001491774727 Computational Analysis and Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.####Neutralization assays with monoclonal antibodies were also performed. Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies.##Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Africa(0.0000399656295585796),Asia(0.0000337090771803031),Europe(0.0000165921570896871),NorthAmerica(0.00000748172588452704),SouthAmerica(0.000031643900638152)
22976A>G 1 22976 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 I472V None - None 1 Tolerated -1.71 2.63294 0.00787402 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_STEIYQAGSTPCNGV Surface glycoprotein_LKPFERDISTEIYQA 14 Surface glycoprotein_KPFERDISTEI -1 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.00001491774727 Computational Analysis and Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.####Neutralization assays with monoclonal antibodies were also performed. Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies.##Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000399656295585796),Asia(0.0000337090771803031),Europe(0.0000165921570896871),NorthAmerica(0.00000748172588452704),SouthAmerica(0.000031643900638152) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85987&&LOCATION=1:22976:A:G
22879C>A 1 22879 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Chen, J., Wang, R., Wang, M., & Wei, G.-W. (2020). Mutations Strengthened SARS-CoV-2 Infectivity. Journal of Molecular Biology, 432(19), 5212–5226. https://doi.org/10.1016/j.jmb.2020.07.009 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375973/ Mutations Strengthened SARS-CoV-2 Infectivity##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity##Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants##Structural Genetics of circulating variants affecting the SARS-CoV-2 Spike / human ACE2 complex##The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity Jiahui Chen, Rui Wang, Menglun Wang and Guo-Wei Wei##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Emma C Thomson, Laura E Rosen, James G Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A Wojcechowskyj, Chris Davis, Luca Piccoli, David J Pascall, Josh Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Aine O'Toole, Dora Pinto, Rachel M Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B Sreenu, Jay Nix, Ruth F Jarrett, Martina Beltramello, Kyriaki Nomikou, Matteo Pizzuto, Lily Tong, Elisabetta Cameroni, Natasha Johnson, Arthur Wickenhagen, Alessandro Ceschi, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Malcolm G Semple, Peter JM Openshaw, Kenneth Baillie, The ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) consortium, Suzannah J Rihn, Samantha J Lycett, Herbert W Virgin, Amalio Telenti, Davide Corti, David L Robertson, Gyorgy Snell Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85869&&LOCATION=1:22879:C:A
22879C>G 1 22879 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Chen, J., Wang, R., Wang, M., & Wei, G.-W. (2020). Mutations Strengthened SARS-CoV-2 Infectivity. Journal of Molecular Biology, 432(19), 5212–5226. https://doi.org/10.1016/j.jmb.2020.07.009 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375973/ Mutations Strengthened SARS-CoV-2 Infectivity##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity##Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants##Structural Genetics of circulating variants affecting the SARS-CoV-2 Spike / human ACE2 complex##The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity Jiahui Chen, Rui Wang, Menglun Wang and Guo-Wei Wei##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Emma C Thomson, Laura E Rosen, James G Shepherd, Roberto Spreafico, Ana da Silva Filipe, Jason A Wojcechowskyj, Chris Davis, Luca Piccoli, David J Pascall, Josh Dillen, Spyros Lytras, Nadine Czudnochowski, Rajiv Shah, Marcel Meury, Natasha Jesudason, Anna De Marco, Kathy Li, Jessica Bassi, Aine O'Toole, Dora Pinto, Rachel M Colquhoun, Katja Culap, Ben Jackson, Fabrizia Zatta, Andrew Rambaut, Stefano Jaconi, Vattipally B Sreenu, Jay Nix, Ruth F Jarrett, Martina Beltramello, Kyriaki Nomikou, Matteo Pizzuto, Lily Tong, Elisabetta Cameroni, Natasha Johnson, Arthur Wickenhagen, Alessandro Ceschi, Daniel Mair, Paolo Ferrari, Katherine Smollett, Federica Sallusto, Stephen Carmichael, Christian Garzoni, Jenna Nichols, Massimo Galli, Joseph Hughes, Agostino Riva, Antonia Ho, Malcolm G Semple, Peter JM Openshaw, Kenneth Baillie, The ISARIC4C Investigators, COVID-19 Genomics UK (COG-UK) consortium, Suzannah J Rihn, Samantha J Lycett, Herbert W Virgin, Amalio Telenti, Davide Corti, David L Robertson, Gyorgy Snell Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8586a&&LOCATION=1:22879:C:G
22879C>A 1 22879 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>G 1 22879 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>A 1 22879 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Ortuso, F., Mercatelli, D., Guzzi, P. H., & Giorgi, F. M. (n.d.). Structural Genetics of circulating variants affecting the SARS-CoV-2 Spike / human ACE2 complex. https://doi.org/10.1101/2020.09.09.289074 https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1886175 Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>G 1 22879 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Ortuso, F., Mercatelli, D., Guzzi, P. H., & Giorgi, F. M. (n.d.). Structural Genetics of circulating variants affecting the SARS-CoV-2 Spike / human ACE2 complex. https://doi.org/10.1101/2020.09.09.289074 https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1886175 Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>A 1 22879 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Thomson, E. C., Rosen, L. E., Shepherd, J. G., Spreafico, R., da Silva Filipe, A., Wojcechowskyj, J. A., Davis, C., Piccoli, L., Pascall, D. J., Dillen, J., Lytras, S., Czudnochowski, N., Shah, R., Meury, M., Jesudason, N., De Marco, A., Li, K., Bassi, J., O’Toole, A., … COVID-19 Genomics UK (COG-UK) consortium. (n.d.). The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity. https://doi.org/10.1101/2020.11.04.355842 https://www.sciencedirect.com/science/article/pii/S0092867421000805?via%3Dihub Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>G 1 22879 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Thomson, E. C., Rosen, L. E., Shepherd, J. G., Spreafico, R., da Silva Filipe, A., Wojcechowskyj, J. A., Davis, C., Piccoli, L., Pascall, D. J., Dillen, J., Lytras, S., Czudnochowski, N., Shah, R., Meury, M., Jesudason, N., De Marco, A., Li, K., Bassi, J., O’Toole, A., … COVID-19 Genomics UK (COG-UK) consortium. (n.d.). The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity. https://doi.org/10.1101/2020.11.04.355842 https://www.sciencedirect.com/science/article/pii/S0092867421000805?via%3Dihub Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>A 1 22879 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
22879C>G 1 22879 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N439K None - None 0.93 Tolerated -3.06 -1.61197 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.008144651253 Computational Analysis and Experimental Binding free energy calculation , Cell line studies and site directed mutagenesis##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene. This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR##The study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain##Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations that conferred complete or partial resistance to C135 were at positions R346, N439, N440, K444, V445 and G446.##Also, N439K is found to minimally modify the Spike-ACE2 recognition. N439K variant stood out from other circulating RBD variants as having a plausible mechanism for maintainence of viral fitness. N439K variant exhibits a 2 fold enhanced binding affinity to human ACE2 receptor Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Africa(0.000739364146833723),Asia(0.0102205922010679),Europe(0.0134032254344009),NorthAmerica(0.000200759644568142),Oceania(0.0141151182230714),SouthAmerica(0.000253151205105216)
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N501V None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0000004387572727 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. N501V mutations is found to decrease the stability with a ddG value of -1.02 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang NorthAmerica(0.00000124695431408784) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22524A>T 1 22524 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q321 None - None 0.08 Tolerated -2.46 -0.215181 0 NA NA NA NA NA Surface glycoprotein_SNFRVQPTESIVRFP 16 Surface glycoprotein_QPTESIVRF 0.02 NA NA nCoV-2019_75_LEFT NA NA NA NA No co - mutations reported NA 0 Computational Analysis and Experimental Sequence alignments followed by Secondary structure predictions and protein dynamics study##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Effect of the mutations on the structural dynamics of Spike glycoprotein were measured using the differences of free energy (ΔΔG) between wild-type and mutant. The ΔΔG, as a consequence of mutation, correlates with the structural changes in three-dimensional structure of protein, and, thus, measures the effect of mutation on protein stability. Q271R was predicted to stabilize the protein structure with the ΔΔG value of 0.379 kcal/mol.##Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an increased infectivity compared to the reference strain via cell line studies Chand, G. B., Banerjee, A., & Azad, G. K. (2020). Identification of twenty-five mutations in Surface glycoprotein (Spike) of SARS-CoV-2 among Indian isolates and their impact on protein dynamics. Gene Reports, 21, 100891. https://doi.org/10.1016/j.genrep.2020.100891 https://pubmed.ncbi.nlm.nih.gov/33015411/ Identification of twenty-five mutations in Surface glycoprotein (Spike) of SARS-CoV-2 among Indian isolates and their impact on protein dynamics Gyanendra Bahadur Chand , Atanu Banerjee , Gajendra Kumar Azad##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8548e&&LOCATION=1:22524:A:T
22524A>T 1 22524 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q321 None - None 0.08 Tolerated -2.46 -0.215181 0 NA NA NA NA NA Surface glycoprotein_SNFRVQPTESIVRFP 16 Surface glycoprotein_QPTESIVRF 0.02 NA NA nCoV-2019_75_LEFT NA NA NA NA No co - mutations reported NA 0 Computational Analysis and Experimental Sequence alignments followed by Secondary structure predictions and protein dynamics study##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Effect of the mutations on the structural dynamics of Spike glycoprotein were measured using the differences of free energy (ΔΔG) between wild-type and mutant. The ΔΔG, as a consequence of mutation, correlates with the structural changes in three-dimensional structure of protein, and, thus, measures the effect of mutation on protein stability. Q271R was predicted to stabilize the protein structure with the ΔΔG value of 0.379 kcal/mol.##Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an increased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity 0
23039C>A 1 23039 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493K None - None 0.47 Tolerated -3.3 -2.11137 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00003290679545 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking##This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. ####Neutralization assays with monoclonal antibodies were also performed. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in Q493 residue might potentially alter viral binding properties.#Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Africa(0.0000399656295585796),Asia(0.0000101127231540909),Europe(0.0000356124347290845),NorthAmerica(0.0000355381979515035)
23039C>A 1 23039 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493K None - None 0.47 Tolerated -3.3 -2.11137 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00003290679545 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking##This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. ####Neutralization assays with monoclonal antibodies were also performed. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in Q493 residue might potentially alter viral binding properties.#Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020a). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design#Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants##Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000399656295585796),Asia(0.0000101127231540909),Europe(0.0000356124347290845),NorthAmerica(0.0000355381979515035) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a45&&LOCATION=1:23039:C:A
23039C>A 1 23039 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493K None - None 0.47 Tolerated -3.3 -2.11137 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00003290679545 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking##This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. ####Neutralization assays with monoclonal antibodies were also performed. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in Q493 residue might potentially alter viral binding properties.#Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Africa(0.0000399656295585796),Asia(0.0000101127231540909),Europe(0.0000356124347290845),NorthAmerica(0.0000355381979515035)
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493M None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. Q493M mutations is found to increase the stability with a ddG value of -0.82 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
23040A>G 1 23040 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493R None - None 0.32 Tolerated -3.3 -2.11137 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00005528341636 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking##This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in Q493 residue might potentially alter viral binding properties.#Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Wang, D., Mai, J., Zhou, W., Yu, W., Zhan, Y., Wang, N., Epstein, N. D., & Yang, Y. (2020a). Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines, 8(3), 355. https://doi.org/10.3390/vaccines8030355 https://pubmed.ncbi.nlm.nih.gov/32635180/ Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design##Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Dongliang Wang , Jinhui Mai , Wenfeng Zhou , Wanting Yu , Yang Zhan , Naidong Wang , Neal D. Epstein and Yi Yang##Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Asia(0.0000168545385901516),Europe(0.000047348350719351),NorthAmerica(0.0000791815989445779),SouthAmerica(0.000031643900638152) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a49&&LOCATION=1:23040:A:G
23040A>G 1 23040 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493R None - None 0.32 Tolerated -3.3 -2.11137 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00005528341636 Computational Analysis and Experimental B and T cell Epitope prediction followed by Peptide Modeling and Molecular Docking##This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in Q493 residue might potentially alter viral binding properties.#Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Asia(0.0000168545385901516),Europe(0.000047348350719351),NorthAmerica(0.0000791815989445779),SouthAmerica(0.000031643900638152)
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q498W None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. Q498W mutation is found to increase the stabilty with a ddG value of -3.66. Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22782G>T 1 22782 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R408I None - None 0.14 Tolerated 1.65 2.13354 0.370079 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0002935286154 Computational Analysis and Experimental Computational Mutation calling followed by Phylogenetic analysis and Antigenic Epitope prediction. Neutralization assays with monoclonal antibodies were also performed. Effect of antigenecity of Spike protein due to a range of variations checked using EMBOSS Antigenic Software reveled that this mutation was one among the range of variations that resulted in decreased antigenicity of the Spike protein epitopes.##Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Africa(0.000139879703455029),Asia(0.00218434820128364),Europe(0.000182513727986558),NorthAmerica(0.000142152791806014),SouthAmerica(0.000042191867517536)
22782G>T 1 22782 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R408I None - None 0.14 Tolerated 1.65 2.13354 0.370079 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0002935286154 Computational Analysis and Experimental Computational Mutation calling followed by Phylogenetic analysis and Antigenic Epitope prediction. Neutralization assays with monoclonal antibodies were also performed. Effect of antigenecity of Spike protein due to a range of variations checked using EMBOSS Antigenic Software reveled that this mutation was one among the range of variations that resulted in decreased antigenicity of the Spike protein epitopes.##Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Khan, M. I., Khan, Z. A., Baig, M. H., Ahmad, I., Farouk, A.-E. A., Song, Y. G., & Dong, J.-J. (2020). Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight. PLOS ONE, 15(9), e0238344. https://doi.org/10.1371/journal.pone.0238344 https://pubmed.ncbi.nlm.nih.gov/32881907/ Africa(0.000139879703455029),Asia(0.00218434820128364),Europe(0.000182513727986558),NorthAmerica(0.000142152791806014),SouthAmerica(0.000042191867517536)
22782G>T 1 22782 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R408I None - None 0.14 Tolerated 1.65 2.13354 0.370079 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0002935286154 Computational Analysis and Experimental Computational Mutation calling followed by Phylogenetic analysis and Antigenic Epitope prediction. Neutralization assays with monoclonal antibodies were also performed. Effect of antigenecity of Spike protein due to a range of variations checked using EMBOSS Antigenic Software reveled that this mutation was one among the range of variations that resulted in decreased antigenicity of the Spike protein epitopes.##Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Singh, P. K., Kulsum, U., Rufai, S. B., Mudliar, S. R., & Singh, S. (2020). Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development. Journal of Laboratory Physicians, 12(02), 154–160. https://doi.org/10.1055/s-0040-1715790 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462717/ Mutations in SARS-CoV-2 Leading to Antigenic Variations in Spike Protein: A Challenge in Vaccine Development##Comparative genome analysis of novel coronavirus (SARS-CoV-2) from different geographical locations and the effect of mutations on major target proteins: An in silico insight##Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Praveen Kumar Sing, Umay Kulsum, Syed Beenish Rufai, S. Rashmi Mudliar, Sarman Singh##Mohd Imran Khan, Zainul A Khan, Mohammad Hassan Baig, Irfan Ahmad, Abd-ElAziem Farouk, Young Goo Song, Jae-Jun Dong##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.000139879703455029),Asia(0.00218434820128364),Europe(0.000182513727986558),NorthAmerica(0.000142152791806014),SouthAmerica(0.000042191867517536) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=606412809d714f1000207dfa&&LOCATION=1:22785:G:T
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S477H None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000000658135909 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. S477H mutations is found to increase the stability with a ddG value of -1.39 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang Asia(0.00000337090771803031),Europe(0.000000809373516570102) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
24378C>T 1 24378 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S939F None - None 0.02 Deleterious 0.74 1.7365 0.0551181 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA Surface glycoprotein_SSTASALGK 0.09 NA NA NA NA NA NA hypermutable low-fitness site Co - mutations reported Co-occuring with 23403A>G (D614G) 0.002777991672 Computational Analysis and Experimental Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR This mutation was identified in the fusion core of the heptad repeat (HR1). In the pre-fusion conformation, the mutated position is located on the second of four non-coaxial helical segments composing the HR1. This mutation is not expected to cause relevant changes in the prefusion structure, although could have a destabilizing effect as a consequence of posing large aromatic residues in direct contact with the solvent.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Ahamad, S., Kanipakam, H., & Gupta, D. (2020). Insights into the structural and dynamical changes of spike glycoprotein mutations associated with SARS-CoV-2 host receptor binding. Journal of Biomolecular Structure and Dynamics, 1–13. https://doi.org/10.1080/07391102.2020.1811774 https://pubmed.ncbi.nlm.nih.gov/32851910/ Africa(0.00363687228983075),Asia(0.00824186937058411),Europe(0.00227595832859513),NorthAmerica(0.00258306586163296),Oceania(0.000429902077860043),SouthAmerica(0.00264753968672538)
24378C>T 1 24378 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S939F None - None 0.02 Deleterious 0.74 1.7365 0.0551181 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA Surface glycoprotein_SSTASALGK 0.09 NA NA NA NA NA NA hypermutable low-fitness site Co - mutations reported Co-occuring with 23403A>G (D614G) 0.002777991672 Computational Analysis and Experimental Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR This mutation was identified in the fusion core of the heptad repeat (HR1). In the pre-fusion conformation, the mutated position is located on the second of four non-coaxial helical segments composing the HR1. This mutation is not expected to cause relevant changes in the prefusion structure, although could have a destabilizing effect as a consequence of posing large aromatic residues in direct contact with the solvent.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Cavallo, L., & Oliva, R. (n.d.). D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly. https://doi.org/10.1101/2020.06.08.140152 https://www.biorxiv.org/content/10.1101/2020.06.08.140152v1.full D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Luigi Cavallo, Romina Oliva##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00363687228983075),Asia(0.00824186937058411),Europe(0.00227595832859513),NorthAmerica(0.00258306586163296),Oceania(0.000429902077860043),SouthAmerica(0.00264753968672538) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef869e6&&LOCATION=1:24378:C:T
24378C>T 1 24378 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S939F None - None 0.02 Deleterious 0.74 1.7365 0.0551181 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA Surface glycoprotein_SSTASALGK 0.09 NA NA NA NA NA NA hypermutable low-fitness site Co - mutations reported Co-occuring with 23403A>G (D614G) 0.002777991672 Computational Analysis and Experimental Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR This mutation was identified in the fusion core of the heptad repeat (HR1). In the pre-fusion conformation, the mutated position is located on the second of four non-coaxial helical segments composing the HR1. This mutation is not expected to cause relevant changes in the prefusion structure, although could have a destabilizing effect as a consequence of posing large aromatic residues in direct contact with the solvent.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.00363687228983075),Asia(0.00824186937058411),Europe(0.00227595832859513),NorthAmerica(0.00258306586163296),Oceania(0.000429902077860043),SouthAmerica(0.00264753968672538)
24390G>C 1 24390 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S943T None - None 0.89 Tolerated -0.241 1.07924 0.787402 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA surface glycoprotein_SSTASALGK 0.09 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 24390G>C 0.00005594155227 Computational Analysis and Experimental Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR S943 is located on a turn immediately downstream the helical segment. S929, D936 and S943 are H-bonded to S1196, R1185 and E1182, respectively. These are all strong H-bonds, especially the one between S943 and E1182, involving a negatively charged residue, and the one between D936 and R1185, being actually a salt bridge estimated to contribute an additional 3-5 kcal/mol to the free energy of protein stability as compare to a neutral H-bond. All these three H-bonds are lost upon mutation, which points to a weakening of the post-fusion assembly.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Ahamad, S., Kanipakam, H., & Gupta, D. (2020). Insights into the structural and dynamical changes of spike glycoprotein mutations associated with SARS-CoV-2 host receptor binding. Journal of Biomolecular Structure and Dynamics, 1–13. https://doi.org/10.1080/07391102.2020.1811774 https://pubmed.ncbi.nlm.nih.gov/32851910/ Africa(0.000199828147792898),Asia(0.000482039803678335),Europe(0.0000105218557154113),NorthAmerica(0.0000386555837367231),SouthAmerica(0.000147671536311376)
24390G>C 1 24390 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S943T None - None 0.89 Tolerated -0.241 1.07924 0.787402 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA surface glycoprotein_SSTASALGK 0.09 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 24390G>C 0.00005594155227 Computational Analysis and Experimental Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR S943 is located on a turn immediately downstream the helical segment. S929, D936 and S943 are H-bonded to S1196, R1185 and E1182, respectively. These are all strong H-bonds, especially the one between S943 and E1182, involving a negatively charged residue, and the one between D936 and R1185, being actually a salt bridge estimated to contribute an additional 3-5 kcal/mol to the free energy of protein stability as compare to a neutral H-bond. All these three H-bonds are lost upon mutation, which points to a weakening of the post-fusion assembly.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Cavallo, L., & Oliva, R. (n.d.). D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly. https://doi.org/10.1101/2020.06.08.140152 https://www.biorxiv.org/content/10.1101/2020.06.08.140152v1.full D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Luigi Cavallo, Romina Oliva##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.000199828147792898),Asia(0.000482039803678335),Europe(0.0000105218557154113),NorthAmerica(0.0000386555837367231),SouthAmerica(0.000147671536311376) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef86a12&&LOCATION=1:24390:G:C
24390G>C 1 24390 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S943T None - None 0.89 Tolerated -0.241 1.07924 0.787402 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA surface glycoprotein_SSTASALGK 0.09 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 24390G>C 0.00005594155227 Computational Analysis and Experimental Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR S943 is located on a turn immediately downstream the helical segment. S929, D936 and S943 are H-bonded to S1196, R1185 and E1182, respectively. These are all strong H-bonds, especially the one between S943 and E1182, involving a negatively charged residue, and the one between D936 and R1185, being actually a salt bridge estimated to contribute an additional 3-5 kcal/mol to the free energy of protein stability as compare to a neutral H-bond. All these three H-bonds are lost upon mutation, which points to a weakening of the post-fusion assembly.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.000199828147792898),Asia(0.000482039803678335),Europe(0.0000105218557154113),NorthAmerica(0.0000386555837367231),SouthAmerica(0.000147671536311376)
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T500R None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0000002193786363 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. T500R mutations is found to increase the stability with a ddG value of -1.23 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang Europe(0.000000404686758285051) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T500W None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. T500W mutations is found to decrease the stability with a ddG value of -1.90 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y489W None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000003071300909 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. Y489W mutations is found to decrease the stability with a ddG value of -1.01 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang Europe(0.00000242812054971031),NorthAmerica(0.00000498781725635136) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505W None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000005265087272 Computational Analysis and Experimental Rosetta Flex ddG calculation is an Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation. Mutations potentially impacting the binding energies were further validated using SPR assay. The affinity between SARS-CoV-2 Spike Protein (RBD His Tag) and hACE2 was measured using a Reichert4SPR system (Reichert Technologies, Depew, NY, USA) in single-cycle mode. Y505W mutations is found to increase the stability with a ddG value of -1.23 Xue, T., Wu, W., Guo, N., Wu, C., Huang, J., Lai, L., Liu, H., Li, Y., Wang, T., & Wang, Y. (n.d.). Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay. https://doi.org/10.1101/2020.12.24.424245 https://www.biorxiv.org/content/10.1101/2020.12.24.424245v1.full.pdf Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay Ting Xue, Weikun Wu, Ning Guo, Chengyong Wu, Jian Huang, Lipeng Lai, Hong Liu, Yalun Li, Tianyuan Wang and Yuxi Wang Europe(0.000000809373516570102),NorthAmerica(0.0000137164974549662) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
Δ27848-28229 1 27848-28229 - ORF8 43740577 https://www.ncbi.nlm.nih.gov/gene/43740577 NC_045512.2:27894-28259 Deletion Deletion ORF8 Protein 121 amino acids QHD43422.1 https://www.ncbi.nlm.nih.gov/protein/QHD43422.1 None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA Computational Analysis and Experimental PCR and Multiplex microbead based Immuno assay####Virus culture, RNA extraction, and sequencing followed by phylogenetic analysis Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00–0·48]) compared with infection with wild-type virus only. In conclusion, the ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines.##A comparison of subgenomic RNA reads predicted from the sequence data suggests that Δ382 viruses may have altered levels of transcription compared to wild-type viruses, including those of the ORF6 and N genes which are known SARS-CoV interferon (IFN) antagonists, raising the possibility that infection with Δ382 viruses might result in an altered innate immune response. Young, B. E., Fong, S.-W., Chan, Y.-H., Mak, T.-M., Ang, L. W., Anderson, D. E., Lee, C. Y.-P., Amrun, S. N., Lee, B., Goh, Y. S., Su, Y. C. F., Wei, W. E., Kalimuddin, S., Chai, L. Y. A., Pada, S., Tan, S. Y., Sun, L., Parthasarathy, P., Chen, Y. Y. C., … Ng, L. F. P. (2020). Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. The Lancet, 396(10251), 603–611. https://doi.org/10.1016/s0140-6736(20)31757-8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434477/ Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study Barnaby E Young, Siew-Wai Fong, Yi-Hao Chan, Tze-Minn Mak, Li Wei Ang, Danielle E Anderson, Cheryl Yi-Pin Lee, Siti Naqiah Amrun, Bernett Lee, Yun Shan Goh, Yvonne C F Su, Wycliffe E Wei, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Yuan Yi Constance Chen, Timothy Barkham, Raymond Tzer Pin Lin, Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, Gavin J D Smith, David Chien Lye, Lisa F P Ng##Yvonne C F Su, Danielle E Anderson, Barnaby E Young, Martin Linster , Feng Zhu, Jayanthi Jayakumar, Yan Zhuang, Shirin Kalimuddin, Jenny G H Low, Chee Wah Tan, Wan Ni Chia , Tze Minn Mak, Sophie Octavia, Jean-Marc Chavatte, Raphael T C Lee , Surinder Pada, Seow Yen Tan, Louisa Sun , Gabriel Z Yan , Sebastian Maurer-Stroh , Ian H Mendenhall , Yee-Sin Leo , David Chien Lye, Lin-Fa Wang, Gavin J D Smith NA https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A27894-28259&hgt.positionInput=NC_045512.2%3A27894-28259&goButton=go&db=wuhCor1&c=NC_045512v2&l=25392&r=26220&pix=950&dinkL=2.0&dinkR=2.0
24368G>T 1 24368 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D936Y None - None 0.01 Deleterious 1.65 4.256 1 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.001434516903 Computational Analysis and Experimentally Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR This mutation was identified in the fusion core of the heptad repeat (HR1). In the pre-fusion conformation, the mutated position is located on the second of four non-coaxial helical segments composing the HR1. This mutation is not expected to cause relevant changes in the prefusion structure, although could have a destabilizing effect as a consequence of posing large aromatic residues in direct contact with the solvent. S929, D936 and S943 are H-bonded to S1196, R1185 and E1182, respectively. These are all strong H-bonds, especially the one between S943 and E1182, involving a negatively charged residue, and the one between D936 and R1185, being actually a salt bridge estimated to contribute an additional 3-5 kcal/mol to the free energy of protein stability as compare to a neutral H-bond. All these three H-bonds are lost upon mutation, which points to a weakening of the post-fusion assembly.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain##Comparisons of MD simulations in the WT and mutants revealed a significant de-stabilization effect of the mutations on RBD and HR1 domains Ahamad, S., Kanipakam, H., & Gupta, D. (2020). Insights into the structural and dynamical changes of spike glycoprotein mutations associated with SARS-CoV-2 host receptor binding. Journal of Biomolecular Structure and Dynamics, 1–13. https://doi.org/10.1080/07391102.2020.1811774 https://pubmed.ncbi.nlm.nih.gov/32851910/ Africa(0.00133884859021242),Asia(0.000728116067094547),Europe(0.00195139954845052),NorthAmerica(0.000848552410736776),Oceania(0.000406018629090041),SouthAmerica(0.000590686145245504)
24368G>T 1 24368 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D936Y None - None 0.01 Deleterious 1.65 4.256 1 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.001434516903 Computational Analysis and Experimentally Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR This mutation was identified in the fusion core of the heptad repeat (HR1). In the pre-fusion conformation, the mutated position is located on the second of four non-coaxial helical segments composing the HR1. This mutation is not expected to cause relevant changes in the prefusion structure, although could have a destabilizing effect as a consequence of posing large aromatic residues in direct contact with the solvent. S929, D936 and S943 are H-bonded to S1196, R1185 and E1182, respectively. These are all strong H-bonds, especially the one between S943 and E1182, involving a negatively charged residue, and the one between D936 and R1185, being actually a salt bridge estimated to contribute an additional 3-5 kcal/mol to the free energy of protein stability as compare to a neutral H-bond. All these three H-bonds are lost upon mutation, which points to a weakening of the post-fusion assembly.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain##Comparisons of MD simulations in the WT and mutants revealed a significant de-stabilization effect of the mutations on RBD and HR1 domains Cavallo, L., & Oliva, R. (n.d.). D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly. https://doi.org/10.1101/2020.06.08.140152 https://www.biorxiv.org/content/10.1101/2020.06.08.140152v1.full D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity##Insights into the structural and dynamical changes of spike glycoprotein mutations associated with SARS-CoV-2 host receptor binding Luigi Cavallo, Romina Oliva##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Shahzaib Ahamad 1, Hema Kanipakam 1, Dinesh Gupta 1 Africa(0.00133884859021242),Asia(0.000728116067094547),Europe(0.00195139954845052),NorthAmerica(0.000848552410736776),Oceania(0.000406018629090041),SouthAmerica(0.000590686145245504) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef869c8&&LOCATION=1:24368:G:T
24368G>T 1 24368 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D936Y None - None 0.01 Deleterious 1.65 4.256 1 NA NA NA NA Surface glycoprotein_VLYENQKLIANQFNSAIGKIQDSLSSTASALG NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.001434516903 Computational Analysis and Experimentally Mutants modelling and analysis using the mutate_model module of the Modeller 9v11 program . Molecular models were analysed and visually inspected with Pymol. The COCOMAPS web server was used to analyse the inter-chain contacts and H-bonds as well as the residues accessibility to the solvent.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR This mutation was identified in the fusion core of the heptad repeat (HR1). In the pre-fusion conformation, the mutated position is located on the second of four non-coaxial helical segments composing the HR1. This mutation is not expected to cause relevant changes in the prefusion structure, although could have a destabilizing effect as a consequence of posing large aromatic residues in direct contact with the solvent. S929, D936 and S943 are H-bonded to S1196, R1185 and E1182, respectively. These are all strong H-bonds, especially the one between S943 and E1182, involving a negatively charged residue, and the one between D936 and R1185, being actually a salt bridge estimated to contribute an additional 3-5 kcal/mol to the free energy of protein stability as compare to a neutral H-bond. All these three H-bonds are lost upon mutation, which points to a weakening of the post-fusion assembly.##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain##Comparisons of MD simulations in the WT and mutants revealed a significant de-stabilization effect of the mutations on RBD and HR1 domains Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.00133884859021242),Asia(0.000728116067094547),Europe(0.00195139954845052),NorthAmerica(0.000848552410736776),Oceania(0.000406018629090041),SouthAmerica(0.000590686145245504)
22930T>C 1 22930 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F456 None - None No co - mutations reported NA 0 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Mutants at this amino acid residue were found to abolish the binding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22927G>C 1 22927 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455F None - None 0.84 Tolerated -3.3 -8.22904 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0003714080313 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012 https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun Africa(0.000199828147792898),Asia(0.000873065098969851),Europe(0.000403068011251911),NorthAmerica(0.000242532614090085),Oceania(0.000620969668020062),SouthAmerica(0.000137123569431992) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858ef&&LOCATION=1:22927:G:C
22927G>T 1 22927 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455F None - None 0.84 Tolerated -3.3 -8.22904 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0003714080313 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012 https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun Africa(0.000199828147792898),Asia(0.000873065098969851),Europe(0.000403068011251911),NorthAmerica(0.000242532614090085),Oceania(0.000620969668020062),SouthAmerica(0.000137123569431992) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858f0&&LOCATION=1:22927:G:T
22927G>C 1 22927 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455F None - None 0.84 Tolerated -3.3 -8.22904 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0003714080313 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Africa(0.000199828147792898),Asia(0.000873065098969851),Europe(0.000403068011251911),NorthAmerica(0.000242532614090085),Oceania(0.000620969668020062),SouthAmerica(0.000137123569431992)
22927G>T 1 22927 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455F None - None 0.84 Tolerated -3.3 -8.22904 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0003714080313 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Africa(0.000199828147792898),Asia(0.000873065098969851),Europe(0.000403068011251911),NorthAmerica(0.000242532614090085),Oceania(0.000620969668020062),SouthAmerica(0.000137123569431992)
22925T>A 1 22925 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455M None - None 0.2 Tolerated -2.14 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000001535650454 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012 https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun Europe(0.0000016187470331402),NorthAmerica(0.00000187043147113176) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858e9&&LOCATION=1:22925:T:A
22925T>A 1 22925 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455M None - None 0.2 Tolerated -2.14 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000001535650454 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Europe(0.0000016187470331402),NorthAmerica(0.00000187043147113176)
22925T>G 1 22925 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455V None - None 0.56 Tolerated -2.14 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000001096893182 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012 https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun Asia(0.00000337090771803031),Europe(0.00000121406027485515),NorthAmerica(0.00000062347715704392) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858eb&&LOCATION=1:22925:T:G
22925T>G 1 22925 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455V None - None 0.56 Tolerated -2.14 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000001096893182 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Asia(0.00000337090771803031),Europe(0.00000121406027485515),NorthAmerica(0.00000062347715704392)
22926T>A 1 22926 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Stop Gain Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455X None - None NA NA -3.3 -0.113764 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012 https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom##Francesco Ortuso, Daniele Mercatelli,Pietro Hiram Guzzi, Federico Manuel Giorgi##Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858ed&&LOCATION=1:22926:T:A
22926T>A 1 22926 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Stop Gain Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L455X None - None NA NA -3.3 -0.113764 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Several ACE2-contact residues exhibit binding-stability tradeoffs, as has been seen in the active sites and binding interfaces of other proteins. Mutations to polar residues at positions L455 would enhance expression but reduce binding, consistent with specific geometric constraints imposed by the close packing of these residues at the ACE2 surface##Mutants at L455 residue were found to abolish the inding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies 0
23059C>G 1 23059 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 P499 None - None No co - mutations reported NA 0 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Mutants at this amino acid residue were found to abolish the binding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22984G>A 1 22984 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q474 None - None No co - mutations reported NA 0 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Mutants at this amino acid residue were found to abolish the binding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22939T>G 1 22939 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S459 None - None No co - mutations reported NA 0 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Deep mutational scanning library yeast surface-display induction and labeling followed by Cell sorting, Sequencing and Phenotype analysis Mutants at this amino acid residue were found to abolish the binding affinity to hACE2 in comparison to wildtype Yi, C., Sun, X., Ye, J. et al. Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies. Cell Mol Immunol 17, 621–630 (2020). https://doi.org/10.1038/s41423-020-0458-z https://www.nature.com/articles/s41423-020-0458-z Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies Chunyan Yi, Xiaoyu Sun, Jing Ye, Longfei Ding, Meiqin Liu, Zhuo Yang, Xiao Lu, Yaguang Zhang, Liyang Ma, Wangpeng Gu, Aidong Qu, Jianqing Xu, Zhengli Shi, Zhiyang Ling & Bing Sun 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
23075T>C 1 23075 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y505H None - None 0.51 Tolerated -2.08 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.00002829984409 Computational Analysis Deep Mutational Scanning of Amino acid mutations in RBD in Spike protein Enhances RBD expression but abolishes Binding affinity Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., King, N. P., Veesler, D., & Bloom, J. D. (2020). Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding. Cell, 182(5), 1295-1310.e20. https://doi.org/10.1016/j.cell.2020.08.012 https://www.sciencedirect.com/science/article/pii/S0092867420310035?dgcid=rss_sd_all Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding Tyler N.Starr, Allison J.Greaney, Sarah K.Hilton, DanielEllis, Katharine H.D.Crawford, Adam S.Dingens, Mary JaneNavarro, John E.Bowen, M. AlejandraTortorici, Alexandra C.Walls, Neil P.King, DavidVeesler, Jesse D.Bloom Asia(0.0000101127231540909),Europe(0.0000445155434113556),NorthAmerica(0.00000810520304157096),SouthAmerica(0.000031643900638152) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85ab7&&LOCATION=1:23075:T:C
26767T>C 1 26767 T C M 43740571 https://www.ncbi.nlm.nih.gov/gene/43740571 NC_045512.2:26523-27191 Single Nucleotide Variation Non Synonymous SNV Membrane glycoprotein 222 amino acids QHD43419.1 https://www.ncbi.nlm.nih.gov/protein/QHD43419.1 I82T B.1.525##B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.525 and B.1.617.2 lineages NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 0.4523541412 Experimental Structural modelling of Spike protein M:I82T mutation lies within TM3, the third of three membrane spanning helices implicated in glucose transport. The frequency of this mutation increased in the USA from 0.014% in October 2020 to 1.62% in February 2021, a 116-fold change. While constituting 0.7% of the isolates overall, M:I82T sub-B.1 lineage accounted for 14.4% of B.1 lineage isolates in February 2021. The rapid emergence of this B.1.I82T clade, recently named Pangolin B.1.575 lineage, suggests that this M gene mutation is more biologically fit, perhaps related to glucose uptake during viral replication. Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1 Africa(0.380872449693264),Asia(0.383828407313521),Europe(0.464280120936591),NorthAmerica(0.464047189739062),Oceania(0.462216384045856),SouthAmerica(0.191487790728337) https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A26523%2D27191&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
28308C>T 28308 C T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 A12G B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.02 Deleterious 1.65 4.256 1 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.002146619957 Experimental Structural modelling of Spike protein A model of the B.1.525 NTD domain, with the Q52R and A67V mutations and H69, V70 and Y144 deletions was built using SwissModel using a PDB coordinate of the Fab C25 complex with the NTD of SARS-CoV-2 (PDB 7m8j) as a template. The complex was minimized and binding energy was estimated using the EvoEF program, part of the EvoDesign pipeline Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Africa(0.0181643786343744),Asia(0.0065395609729788),Europe(0.00160984392445793),NorthAmerica(0.00182928197876686),Oceania(0.000453785526630045),SouthAmerica(0.00005273983439692)
28308C>T 28308 C T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 A12G B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.02 Deleterious 1.65 4.256 1 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.002146619957 Experimental Structural modelling of Spike protein A model of the B.1.525 NTD domain, with the Q52R and A67V mutations and H69, V70 and Y144 deletions was built using SwissModel using a PDB coordinate of the Fab C25 complex with the NTD of SARS-CoV-2 (PDB 7m8j) as a template. The complex was minimized and binding energy was estimated using the EvoEF program, part of the EvoDesign pipeline Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.0181643786343744),Asia(0.0065395609729788),Europe(0.00160984392445793),NorthAmerica(0.00182928197876686),Oceania(0.000453785526630045),SouthAmerica(0.00005273983439692)
29402G>T 1 29402 G T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 D377Y B.1.617.1##B.1.617.2##B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.2##https://outbreak.info/situation-reports?pango=B.1.617.3 Characterisitc mutation of B.1.617.1, B.1.617.2 and B.1.617.3 lineages 0.02 Deleterious 1.65 4.256 1 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 0.4490397687 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 Africa(0.32104390224407),Asia(0.370425678226633),Europe(0.460642796353125),NorthAmerica(0.464862697860476),Oceania(0.464867446859326),SouthAmerica(0.185485997573968)
28461A>G 1 28461 A G N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 D63G B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characterisitc mutation of B.1.617.2 lineage 0.13 Tolerable -2.01 0.143638 0.992126 9b NA NA NA NA NA NA NA NA NA NA nCoV-2019_93_RIGHT NA NA NA NA 0.4359279464 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 Africa(0.321563455428332),Asia(0.360016315193355),Europe(0.447308772354391),NorthAmerica(0.450135543933941),Oceania(0.459278719847146),SouthAmerica(0.186519698328147)
28883G>A 1 28883 G A N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 G204R B.1.1.7## P.1## P.3 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=P.3 Characteristic mutation of B.1.1.7, P.1 and P.3 lineages. 0.03 Deleterious 1.65 4.256 1 NA NA NA Transmembrane Nucleocapsid phosphoprotein_RGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGG NA NA NA NA NA NA NA N gene Forward NA NA NA Variant associated with viral transmission and cell signalling. NA 0.3089809884 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Three‐dimensional structure analysis on I‐tasser, and implication of these mutations analyzed by CUPSAT points out that this mutation reduces protein stability while favouring torsion. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Africa(0.192694282916692),Asia(0.420301628822609),Europe(0.323823059618049),NorthAmerica(0.247385760280515),Oceania(0.377095772629568),SouthAmerica(0.647159959917726)
28883G>C 1 28883 G C N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 G204R B.1.1.7## P.1## P.3 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=P.3 Characteristic mutation of B.1.1.7, P.1 and P.3 lineages. 0.03 Deleterious 1.65 4.256 1 NA NA NA Transmembrane Nucleocapsid phosphoprotein_RGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGG NA NA NA NA NA NA NA N gene Forward NA NA NA Variant associated with viral transmission and cell signalling. Functional consequences induced by co - occurring mutations 28881G>A | 28882G>A 0.3089809884 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Three‐dimensional structure analysis on I‐tasser, and implication of these mutations analyzed by CUPSAT points out that this mutation reduces protein stability while favouring torsion.##The triple site mutation 28881-28883 that brings change in two amino acid 203-204:RG>KR, is known to play a critical role in virion assembly and structure. The mutated 203/204 region of N protein affects the SR (serine-arginine)-rich motif of the protein (a crucial region for controlling viral transcription and replication) by introducing lysin in between them that might hamper the phosphorylation at serine residue required for normal functioning of N protein. Significant reduction in pathogenicity has been observed with the deletion of SR domain, therefore it is important to target 203-204:RG>KR positions of the N protein to design the drugs for controlling the disease. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Africa(0.192694282916692),Asia(0.420301628822609),Europe(0.323823059618049),NorthAmerica(0.247385760280515),Oceania(0.377095772629568),SouthAmerica(0.647159959917726)
28512C>G 1 28512 C G N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 P80R P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1 lineage NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0212327807 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055##Faria, N. R., Mellan, T. A., Whittaker, C., Claro, I. M., Candido, D., Mishra, S., Crispim, M., Sales, F., Hawryluk, I., McCrone, J. T., Hulswit, R., Franco, L., Ramundo, M. S., de Jesus, J. G., Andrade, P. S., Coletti, T. M., Ferreira, G. M., Silva, C., Manuli, E. R., Pereira, R., … Sabino, E. C. (2021). Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science (New York, N.Y.), 372(6544), 815–821. https://doi.org/10.1126/science.abh2644##Wang, P., Casner, R. G., Nair, M. S., Wang, M., Yu, J., Cerutti, G., Liu, L., Kwong, P. D., Huang, Y., Shapiro, L., & Ho, D. D. (2021). Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell host & microbe, 29(5), 747–751.e4. https://doi.org/10.1016/j.chom.2021.04.007##Romano, C. M., Felix, A. C., Paula, A. V., Jesus, J. G., Andrade, P. S., Cândido, D., Oliveira, F. M., Ribeiro, A. C., Silva, F., Inemami, M., Costa, A. A., Leal, C., Figueiredo, W. M., Pannuti, C. S., Souza, W. M., Faria, N. R., & Sabino, E. C. (2021). SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo, 63, e36. https://doi.org/10.1590/S1678-9946202163036##de Siqueira, I. C., Camelier, A. A., Maciel, E., Nonaka, C., Neves, M., Macêdo, Y., de Sousa, K., Araujo, V. C., Paste, A. A., Souza, B., & Gräf, T. (2021). Early detection of P.1 variant of SARS-CoV-2 in a cluster of cases in Salvador, Brazil. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, S1201-9712(21)00411-2. Advance online publication. https://doi.org/10.1016/j.ijid.2021.05.010 https://pubmed.ncbi.nlm.nih.gov/33852911/##https://pubmed.ncbi.nlm.nih.gov/33853970/##https://pubmed.ncbi.nlm.nih.gov/33887205/##https://pubmed.ncbi.nlm.nih.gov/33909850/##https://pubmed.ncbi.nlm.nih.gov/33989776/ Antibody evasion by the P.1 strain of SARS-CoV-2##Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil##Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization##SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil##Early detection of P.1 variant of SARS-CoV-2 in a cluster of cases in Salvador, Brazil Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.000859261035509462),Asia(0.000724745159376517),Europe(0.00423180943138678),NorthAmerica(0.0292822281577248),Oceania(0.000429902077860043),SouthAmerica(0.412288381414482)
28881G>A 1 28881 G A N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 R203K B.1.1.7## P.1## P.3 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=P.3 Characteristic mutation of B.1.1.7, P.1 and P.3 lineages. 0 Deleterious 1.65 4.256 1 NA NA NA Transmembrane Nucleocapsid phosphoprotein_RGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGG NA NA NA NA NA NA NA N gene Forward NA NA NA Variant associated with viral transmission and cell signalling. Functional consequences induced by co - occurring mutations 28882G>A | 28883G>C 0.3270637113 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Arginine is a chiral and polar amino acid which frequently occurs at the N‐termini of alpha helices while lysine is a chiral and polar amino acid. Using the three‐dimensional structure on I‐tasser, the implication of these mutations has been analyzed by CUPSAT. The results points out that this mutation reduces protein stability while favouring torsion.##The triple site mutation 28881-28883 that brings change in two amino acid 203-204:RG>KR, is known to play a critical role in virion assembly and structure. The mutated 203/204 region of N protein affects the SR (serine-arginine)-rich motif of the protein (a crucial region for controlling viral transcription and replication) by introducing lysin in between them that might hamper the phosphorylation at serine residue required for normal functioning of N protein. Significant reduction in pathogenicity has been observed with the deletion of SR domain, therefore it is important to target 203-204:RG>KR positions of the N protein to design the drugs for controlling the disease. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Africa(0.198589213276582),Asia(0.421505042877946),Europe(0.356606329219962),NorthAmerica(0.247774186549353),Oceania(0.379460234057798),SouthAmerica(0.647624070460419)
28881G>T 1 28881 G T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 R203M B.1.617.1##B.1.617.2##B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.2##https://outbreak.info/situation-reports?pango=B.1.617.3 Characterisitc mutation of B.1.617.1, B.1.617.2 and B.1.617.3 lineages 0 Deleterious 1.65 4.256 1 NA NA NA Transmembrane Nucleocapsid phosphoprotein_RGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGG NA NA NA NA NA NA NA NA NA NA NA 0.4459171332 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 Africa(0.325320224606838),Asia(0.379442856372364),Europe(0.460716854029891),NorthAmerica(0.454072802180674),Oceania(0.462120850250776),SouthAmerica(0.186699013765097)
28887C>T 1 28887 C T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 T205I B.1.351##B.1.525##B.1.427/B.1.429##B.1.621 https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.351,B.1.427/B.1.429 and B.1.621 lineages 0.09 Tolerated -1.87 -0.0880472 0.905512 NA NA NA Transmembrane Nucleocapsid phosphoprotein_RGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGG NA NA NA NA NA NA NA N gene Forward NA NA NA No co - mutations reported NA 0.03550401913 Experimental Structural modelling of Spike protein The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence.##A model of the B.1.525 NTD domain, with the Q52R and A67V mutations and H69, V70 and Y144 deletions was built using SwissModel using a PDB coordinate of the Fab C25 complex with the NTD of SARS-CoV-2 (PDB 7m8j) as a template. The complex was minimized and binding energy was estimated using the EvoEF program, part of the EvoDesign pipeline Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Africa(0.274763703215235),Asia(0.0406834852489078),Europe(0.0118472048487949),NorthAmerica(0.062617057836235),Oceania(0.0260568426080726),SouthAmerica(0.0550814830441432)
28887C>T 1 28887 C T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Non Synonymous SNV Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 T205I B.1.351##B.1.525##B.1.427/B.1.429##B.1.621 https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.351,B.1.427/B.1.429 and B.1.621 lineages 0.09 Tolerated -1.87 -0.0880472 0.905512 NA NA NA Transmembrane Nucleocapsid phosphoprotein_RGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGG NA NA NA NA NA NA NA N gene Forward NA NA NA No co - mutations reported NA 0.03550401913 Experimental Structural modelling of Spike protein The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence.##A model of the B.1.525 NTD domain, with the Q52R and A67V mutations and H69, V70 and Y144 deletions was built using SwissModel using a PDB coordinate of the Fab C25 complex with the NTD of SARS-CoV-2 (PDB 7m8j) as a template. The complex was minimized and binding energy was estimated using the EvoEF program, part of the EvoDesign pipeline Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.274763703215235),Asia(0.0406834852489078),Europe(0.0118472048487949),NorthAmerica(0.062617057836235),Oceania(0.0260568426080726),SouthAmerica(0.0550814830441432)
28281A>T 28281 A T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Deletion Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 Δ3 B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.01 Deleterious 1.65 2.29773 1 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 0 Experimental Structural modelling of Spike protein The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence.##A model of the B.1.525 NTD domain, with the Q52R and A67V mutations and H69, V70 and Y144 deletions was built using SwissModel using a PDB coordinate of the Fab C25 complex with the NTD of SARS-CoV-2 (PDB 7m8j) as a template. The complex was minimized and binding energy was estimated using the EvoEF program, part of the EvoDesign pipeline Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria
28281A>T 28281 A T N 43740575 https://www.ncbi.nlm.nih.gov/gene/43740575 NC_045512.2:28274-29533 Single Nucleotide Variation Deletion Nucleocapsid phosphoprotein 419 amino acids QHD43423.2 https://www.ncbi.nlm.nih.gov/protein/1798172432 Δ3 B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.01 Deleterious 1.65 2.29773 1 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA 0 Experimental Structural modelling of Spike protein The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence.##A model of the B.1.525 NTD domain, with the Q52R and A67V mutations and H69, V70 and Y144 deletions was built using SwissModel using a PDB coordinate of the Fab C25 complex with the NTD of SARS-CoV-2 (PDB 7m8j) as a template. The complex was minimized and binding energy was estimated using the EvoEF program, part of the EvoDesign pipeline Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo
7296C>T 1 7296 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 A2344V B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.617.3 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
10634G>T 1 10634 G T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 A3457S B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.617.3 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
11322C>T 1 11322 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 A3686V B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.617.3 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
17259G>T 1 17259 G T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 E1264D P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1. lineage Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A266%2D21555&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
15451G>A 1 15451 G A ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 G662S B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.2 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
5648A>C 1 5648 A C ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 K1795Q P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1. lineage Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A266%2D21555&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
20396A>G 1 20396 A G ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 K2310R B.1.617.1 https://outbreak.info/situation-reports?pango=B.1.617.1 Characteristic mutation of B.1.617.1 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
17523G>T 1 17523 G T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 M1352I B.1.617.1 https://outbreak.info/situation-reports?pango=B.1.617.1 Characteristic mutation of B.1.617.1 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
16466C>T 1 16466 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 P1000L B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.2 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
1 ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 P314F B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A266%2D21555&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
14408C>T 1 14408 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 P314L B.1.1.7##B.1.351##P.1##B.1.427/B.1.429##P.3##B.1.616##B.1.617.1##B.1.617.2##B.1.617.3##B.1.620##B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.2##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7##B.1.351##P.1##B.1.427/B.1.429##P.3##B.1.616##B.1.617.1##B.1.617.2##B.1.617.3##B.1.620##B.1.621 lineages Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2
14408C>T 1 14408 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 P314L B.1.1.7##B.1.351##P.1##B.1.427/B.1.429##P.3##B.1.616##B.1.617.1##B.1.617.2##B.1.617.3##B.1.620##B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.2##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7##B.1.351##P.1##B.1.427/B.1.429##P.3##B.1.616##B.1.617.1##B.1.617.2##B.1.617.3##B.1.620##B.1.621 lineages Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees
3828C>T 1 3828 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 S1188L P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1. lineage Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A266%2D21555&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
4965C>T 1 4965 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 T1567I B.1.617.1 https://outbreak.info/situation-reports?pango=B.1.617.1 Characteristic mutation of B.1.617.1 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
6285C>T 1 6285 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 T2007I B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086##Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33990970/##https://pubmed.ncbi.nlm.nih.gov/33880483/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report##High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A266%2D21555&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
8208C>T 1 8208 C T ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 T2648I B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.617.3 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
11201A>G 1 11201 A G ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Non Synonymous SNV ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 T3646A B.1.617.1 https://outbreak.info/situation-reports?pango=B.1.617.1 Characteristic mutation of B.1.617.1 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
25469C>T 1 25469 C T ORF3a 43740569 https://www.ncbi.nlm.nih.gov/gene/43740569 NC_045512.2:25393-26220 Single Nucleotide Variation Non Synonymous SNV ORF3a Protein 275 amino acids QHD43417.1 https://www.ncbi.nlm.nih.gov/protein/QHD43417.1 S26L B.1.617.1##B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.1 and B.1.617.2 lineages Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
27206 ORF6 43740569 https://www.ncbi.nlm.nih.gov/gene/43740569 NC_045512.2:25393-26220 Deletion Deletion ORF6 Protein 61 amino acids QHD43420.1 https://www.ncbi.nlm.nih.gov/protein/QHD43420.1 Δ2-3FH>LX B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation ofB.1.525lineage Experimental Structural modelling of Spike protein Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria
27206 ORF6 43740569 https://www.ncbi.nlm.nih.gov/gene/43740569 NC_045512.2:25393-26220 Deletion Deletion ORF6 Protein 61 amino acids QHD43420.1 https://www.ncbi.nlm.nih.gov/protein/QHD43420.1 Δ2-3FH>LX B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation ofB.1.525lineage Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo
Δ27264-27290 1 27264-27290 TTTTAAAGTTTCCATTTGGAATCTTGA - ORF6 43740569 https://www.ncbi.nlm.nih.gov/gene/43740569 NC_045512.2:25393-26220 Deletion In frame Deletion ORF6 Protein 61 amino acids QHD43420.1 https://www.ncbi.nlm.nih.gov/protein/QHD43420.1 ΔFKVSIWNLD None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA Experimental SARS-CoV-2 Hong Kong/VM20001061/2020 was isolated from a nasopharyngeal aspirate and throat swab from 39-year-old male patient in Hong Kong and passaged 5 times in African green monkey (Cercopithecus aethiops) kidney epithelial cells (Vero E6) cells. Genomic RNA was extracted, which was followed by sequencing, alignment and protein structure prediction. This mutation was predicted to manifest as an in-frame deletion of 9 aa ΔFKVSIWNLD (SARS-CoV-2 p6Δ22-30). The function of p6 in SARS-CoV-2 has not yet been fully determined. However, based on its similarity to the SARS-CoV p6, it appears likely that it plays a role as an antagonist of interferon signaling, thus assisting in the viral suppression of the innate immune system. Riojas, M. A., Frank, A. M., Puthuveetil, N. P., Flores, B., Parker, M., King, S. P., Peiris, M., Chu, D. K. W., Benton, B., Bradford, R., Hazbón, M. H., & Rashid, S. (2020). A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein. bioRxiv : The Preprint Server for Biology. https://doi.org/10.1101/2020.06.09.134460 https://www.biorxiv.org/content/10.1101/2020.06.09.134460v1.full.pdf+html A Rare Deletion in SARS-CoV-2 ORF6 Dramatically Alters the Predicted Three-Dimensional Structure of the Resultant Protein Marco A. Riojas, Andrew M. Frank, Nikhita P. Puthuveetil, Beth Flores, Michael Parker, Stephen P. King, Malik Peiris, Daniel K. W. Chu, Briana Benton, Rebecca Bradford, Manzour Hernando Hazbón, Sujatha Rashid https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A25393%2D26220&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E
Δ27387-27756 ORF7a 43740573 https://www.ncbi.nlm.nih.gov/gene/43740573 NC_045512.2 27394.-27759 Deletion Deletion ORF7a Protein 121 aa QNH88665.1 https://www.ncbi.nlm.nih.gov/protein/QNH88665.1 370-nucleotide deletion Experimental This major deletion was confirmed independently by long-range PCR and Sanger sequencing (with primers 5′-AACTCGTAATCGGAGCTGTGA-3′ and 5′-TGTCATTCTCCTAAGAAGCTATTAAA-3′). The entire ORF7a and the original stop codon for ORF6 were lost. The latter resulted in an extension of the Orf6 protein by 2 amino acids. Furthermore, ORF7b was potentially extended in the 5′ direction by 27 nucleotides due to the occurrence of an in-frame start codon. The repeated reemergence of ORF7a deletion variants may suggest that the accessory protein could impose a fitness cost that exceeds the benefits of its canonical function in certain situations. Tse, H., Wong, S. C., Ip, K. F., Cheng, V. C., To, K. K., Lung, D. C., & Choi, G. K. (2021). Genome Sequences of Three SARS-CoV-2 ORF7a Deletion Variants Obtained from Patients in Hong Kong. Microbiology resource announcements, 10(15), e00251-21. https://doi.org/10.1128/MRA.00251-21 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050975/ Genome Sequences of Three SARS-CoV-2 ORF7a Deletion Variants Obtained from Patients in Hong Kong
27638T>C 27638 T C ORF7a 43740573 https://www.ncbi.nlm.nih.gov/gene/43740573 NC_045512.2 27394.-27759 Single Nucleotide Variation Non Synonymous SNV ORF7a Protein 121 aa QNH88665.1 https://www.ncbi.nlm.nih.gov/protein/QNH88665.1 V82A B.1.617.1##B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.671.1 and B.1.617.3 lineages Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
28247AGATTT>A 28247 AGATTT A ORF8 43740577 https://www.ncbi.nlm.nih.gov/gene/43740577 NC_045512.2:27894-28259 Single Nucleotide Variation Deletion ORF8 Protein 121 amino acids QHD43422.1 https://www.ncbi.nlm.nih.gov/protein/QHD43422.1 Δ119-120 B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.2 lineage Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2
Δ28090 -28095 28090 - 28095 - ORF8 43740577 https://www.ncbi.nlm.nih.gov/gene/43740577 NC_045512.2:27894-28259 Single Nucleotide Variation Non Synonymous SNV ORF8 Protein 121 amino acids QHD43422.1 https://www.ncbi.nlm.nih.gov/protein/QHD43422.1 None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA Experimental Structural modelling of Spike protein Deletion predicted to significantly impact ORF8 protein structure and function Pereira F. (2020). Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 85, 104525. https://doi.org/10.1016/j.meegid.2020.104525 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467077/ Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene Filipe Pereira https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A27894-28259&hgt.positionInput=NC_045512.2%3A27894-28259&goButton=go&db=wuhCor1&c=NC_045512v2&l=25392&r=26220&pix=950&dinkL=2.0&dinkR=2.0
Δ28254 28254 - ORF8 43740577 https://www.ncbi.nlm.nih.gov/gene/43740577 NC_045512.2:27894-28259 Single Nucleotide Variation Non Synonymous SNV ORF8 Protein 121 amino acids QHD43422.1 https://www.ncbi.nlm.nih.gov/protein/QHD43422.1 None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA Experimental Structural modelling of Spike protein Deletion predicted to significantly impact ORF8 protein structure and function Pereira F. (2020). Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 85, 104525. https://doi.org/10.1016/j.meegid.2020.104525 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467077/ Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene Filipe Pereira https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A27894-28259&hgt.positionInput=NC_045512.2%3A27894-28259&goButton=go&db=wuhCor1&c=NC_045512v2&l=25392&r=26220&pix=950&dinkL=2.0&dinkR=2.0
22604G>A 1 22604 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A348T None - None 0.02 Deleterious 0.753 1.75899 0.80315 disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 Surface glycoprotein_NATRFASVY 0.1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00003159052363 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.00107907199808165),Asia(0.0000303381694622728),Europe(0.0000194249643976824),NorthAmerica(0.0000162104060831419),SouthAmerica(0.000073835768155688) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85572&&LOCATION=1:22604:G:A
22865G>T 1 22865 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A435S None - None 0.5 Tolerated 1.65 4.256 0.913386 disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA NA S Reverse NA NA NA No co - mutations reported NA 0.00006515545499 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Asia(0.0000471927080524244),Europe(0.000100767002812978),NorthAmerica(0.0000199512690254054),SouthAmerica(0.000021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85847&&LOCATION=1:22865:G:T
22986C>T 1 22986 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A475V None - None 0.37 Tolerated 1.56 0.135937 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_STEIYQAGSTPCNGV Surface glycoprotein_LKPFERDISTEIYQA 14 NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000378208769 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.000379673480806506),Asia(0.000121352677849091),Europe(0.000184537161777983),NorthAmerica(0.000740690862568177),Oceania(0.000143300692620014),SouthAmerica(0.000200411370708296) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef859a4&&LOCATION=1:22986:C:T
21762C>T 1 21762 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A67V B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.003888925086 Experimental Structural modelling of Spike protein Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ Africa(0.0233399276622105),Asia(0.00221468637074591),Europe(0.00424516409441018),NorthAmerica(0.00315666484611337),Oceania(0.000764270360640077),SouthAmerica(0.00334370550076473)
21762C>T 1 21762 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A67V B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.003888925086 Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report##High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.0233399276622105),Asia(0.00221468637074591),Europe(0.00424516409441018),NorthAmerica(0.00315666484611337),Oceania(0.000764270360640077),SouthAmerica(0.00334370550076473)
24054C>T 1 24054 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A831V None - None 1 Tolerated 1.65 3.27011 1 NA NA NA NA NA NA 19 Surface glycoprotein_TLADAGFIK -1 Spike glycoprotein FIEDLLFNKVTLADAGF NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occurrinng with 23403A>G (D614G) 0.001575138609 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Foley, B., Giorgi, E. E., Bhattacharya, T., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., LaBranche, C. C., Montefiori, D. C., & on behalf of the Sheffield COVID-19 Genomics Group. (n.d.). Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. https://doi.org/10.1101/2020.04.29.069054 https://www.sciencedirect.com/science/article/pii/S0092867420308205?via%3Dihub Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 Africa(0.000219810962572188),Asia(0.000330348956366971),Europe(0.000450011675212977),NorthAmerica(0.000324831598819882),Oceania(0.0000955337950800096),SouthAmerica(0.000126575602552608)
24054C>T 1 24054 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 A831V None - None 1 Tolerated 1.65 3.27011 1 NA NA NA NA NA NA 19 Surface glycoprotein_TLADAGFIK -1 Spike glycoprotein FIEDLLFNKVTLADAGF NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occurrinng with 23403A>G (D614G) 0.0003856676427 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##B Korber, WM Fischer, S Gnanakaran, H Yoon, J Theiler, W Abfalterer, B Foley, EE Giorgi, T Bhattacharya, MD Parker, DG Partridge, CM Evans, TM Freeman, TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group, CC LaBranche, DC Montefiori Africa(0.000219810962572188),Asia(0.000330348956366971),Europe(0.000450011675212977),NorthAmerica(0.000324831598819882),Oceania(0.0000955337950800096),SouthAmerica(0.000126575602552608) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef86634&&LOCATION=1:24054:C:T
21974G>T 1 21974 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D138Y P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1 lineage 0.02266905263 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.00477589273225027),Asia(0.0036810312280891),Europe(0.00641104762475178),NorthAmerica(0.0302392655937872),Oceania(0.0010031048483401),SouthAmerica(0.396782870101788) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22962A>T 1 22962 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D467V None - None 0.23 Tolerated 1.65 2.25839 0.488189 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_LKPFERDISTEIYQA 14 Surface glycoprotein_KPFERDISTEI -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0000002193786363 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Oceania(0.0000238834487700024) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85958&&LOCATION=1:22962:A:T
1 S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D480G None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0 Experimental Pseudotyped Virus Infectivity analysis. A single SARS-CoV-1 amino acid change, Spike D480A/G in the receptor binding domain (RBD), arose in infected humans and civets and became the dominant variant among 2003/2004 viruses. D480A/G escapes neutralizing antibody 80R, and immune pressure from 80R in vitro could recapitulate emergence of the D480 mutation. Although there is no evidence yet of antigenic drift for SARS-CoV-2, with extended human-to-human transmission, SARS-CoV-2 could also acquire mutations with fitness advantages and immunological resistance. Attending to this risk now by identifying evolutionary transitions that may be relevant to the fitness or antigenic profile of the virus is important to ensure effectiveness of the vaccines and immunotherapeutic interventions as they advance to the clinic. Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., Hastie, K. M., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., Sheffield COVID-19 Genomics Group, McDanal, C., Perez, L. G., … Montefiori, D. C. (2020). Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell, 182(4), 812–827.e19. https://linkinghub.elsevier.com/retrieve/pii/S0092867420308205 Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus Bette Korber, Will M. Fischer, Sandrasegaram Gnanakaran, Celia C. LaBranche, Erica O. Saphire, David C. Montefiori 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://www.sciencedirect.com/science/article/pii/S0092867421004281 Antibody evasion by the P.1 strain of SARS-CoV-2 Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Experimental Structural modelling of Spike protein Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057251.1/ High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Experimental Structural modelling of Spike protein Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilize a specific conformation of the viral spike, within which the key host receptor binding site is more accessible.##614G is associated with higher viral load and younger age of patients Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
23403A>G 1 23403 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D614G B.1.1.7## B.1.351## P.1## B.1.525## B.1.427/B.1.429## P.3## B.1.616## B.1.617.1## B.1.617.2## B.1.617.3## B.1.620## B.1.621 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.616##https://outbreak.info/situation-reports?pango=B.1.617.1##https://docs.google.com/spreadsheets/d/1HiZZ5_9c6eqpjiWd0y4m12XaHRN_0jlQIQ6IZPVFScI/edit#gid=0##https://outbreak.info/situation-reports?pango=B.1.617.3##https://outbreak.info/situation-reports?pango=B.1.620##https://outbreak.info/situation-reports?pango=B.1.621 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, B.1.427/B.1.429, P.3, B.1.616, B.1.617.1, B.1.617.2, B.1.617.3, B.1.620 and B.1.621 lineages. 0.3 Tolerated 1.65 2.25839 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA Multiple co-occurring mutations reported L5F, Q321L, V341I, K458R, I472V, Q675H, A831V, A879S, D936Y, S939F, S943T, M1237I 0.9859121621 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Africa(0.947505145574806),Asia(0.967005555255919),Europe(0.987716138139016),NorthAmerica(0.988960089980223),Oceania(0.939383807021734),SouthAmerica(0.987310795844101)
24077G>T 1 24077 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D839Y None - None 0.02 Deleterious 1.65 4.256 0.992126 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0002957224018 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Foley, B., Giorgi, E. E., Bhattacharya, T., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., LaBranche, C. C., Montefiori, D. C., & on behalf of the Sheffield COVID-19 Genomics Group. (n.d.). Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. https://doi.org/10.1101/2020.04.29.069054 https://www.sciencedirect.com/science/article/pii/S0092867420308205?via%3Dihub Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 Africa(0.0000799312591171592),Asia(0.000101127231540909),Europe(0.000290565092448667),NorthAmerica(0.000322337690191707),Oceania(0.000835920706950084),SouthAmerica(0.000464110542692896)
24077G>T 1 24077 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D839Y None - None 0.02 Deleterious 1.65 4.256 0.992126 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0002957224018 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##B Korber, WM Fischer, S Gnanakaran, H Yoon, J Theiler, W Abfalterer, B Foley, EE Giorgi, T Bhattacharya, MD Parker, DG Partridge, CM Evans, TM Freeman, TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group, CC LaBranche, DC Montefiori Africa(0.0000799312591171592),Asia(0.000101127231540909),Europe(0.000290565092448667),NorthAmerica(0.000322337690191707),Oceania(0.000835920706950084),SouthAmerica(0.000464110542692896) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef86678&&LOCATION=1:24077:G:T
24410G>A 1 24410 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 D950N B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.2 lineage 0.4302023834 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 Africa(0.305357392642328),Asia(0.330807399816623),Europe(0.439536358474768),NorthAmerica(0.451570788349456),Oceania(0.458466682588966),SouthAmerica(0.189842307895153)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Structural modelling of Spike protein Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Structural modelling of Spike protein Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Ramanathan, M., Ferguson, I. D., Miao, W., & Khavari, P. A. (2021). SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. The Lancet. Infectious diseases, S1473-3099(21)00262-0. Advance online publication. https://doi.org/10.1016/S1473-3099(21)00262-0 https://www.sciencedirect.com/science/article/pii/S1473309921002620?via%3Dihub SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Romano, C. M., Felix, A. C., Paula, A. V., Jesus, J. G., Andrade, P. S., Cândido, D., Oliveira, F. M., Ribeiro, A. C., Silva, F., Inemami, M., Costa, A. A., Leal, C., Figueiredo, W. M., Pannuti, C. S., Souza, W. M., Faria, N. R., & Sabino, E. C. (2021). SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo, 63, e36. https://doi.org/10.1590/S1678-9946202163036 https://pubmed.ncbi.nlm.nih.gov/33909850/ SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Wang, P., Casner, R. G., Nair, M. S., Wang, M., Yu, J., Cerutti, G., Liu, L., Kwong, P. D., Huang, Y., Shapiro, L., & Ho, D. D. (2021). Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell host & microbe, 29(5), 747–751.e4. https://doi.org/10.1016/j.chom.2021.04.007 https://pubmed.ncbi.nlm.nih.gov/33887205/ Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
23012G>A 1 23012 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Viruses passaged in the presence of monoclonal antibodies C121, C144 had mutations at positions E484 and Q493. In contrast, virus populations passaged in the presence of monoclonal antibody C135 lacked mutations at E484 or Q493. he E484K and Q493R mutants that emerged during replication in the presence of C121 or C144, both caused apparently complete, or near complete, resistance to both antibodies. However, both of these mutants retained full sensitivity to C135. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. IC50(M) values are shown for each variant. There was no observed neutralization with hIgG1 isotype control Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous##Author links open overlay panelMuthukumarRamanathana†Ian DFergusonb†WeiliMiaob†Paul AKhavarib##David Hodgson 1, Stefan Flasche 1, Mark Jit 1, Adam J Kucharski 1, CMMID COVID-19 Working Group; Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group##Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6##Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef859f3&&LOCATION=1:23012:G:A
22574T>C 1 22574 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F338L None - None 0.11 Tolerated 1.65 2.13354 0.968504 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_RFPNITNLCPF 0.07 Spike glycoprotein VRFPNITNLCPFGEVFN NA NA NA NA NA No co - mutations reported NA 0.0001175869491 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was accessed. Increased sensitivity to convalescent sera. This mutation was found to possess over 4-fold sensitivity to one or two of the ten tested sera. Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000799312591171592),Asia(0.0000404508926163637),Europe(0.000079723291382155),NorthAmerica(0.000198889213097011),Oceania(0.0000238834487700024),SouthAmerica(0.000031643900638152) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85517&&LOCATION=1:22574:T:C
23032T>A 1 23032 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F490L None - None 0.65 Tolerated -3.3 -1.73682 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0002560148686 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00131886577543313),Asia(0.000235963540262122),Europe(0.000300277574647508),NorthAmerica(0.000177067512600473),Oceania(0.0000716503463100072),SouthAmerica(0.000021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a2d&&LOCATION=1:23032:T:A
23032T>G 1 23032 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F490L None - None 0.65 Tolerated -3.3 -1.73682 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0002560148686 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00131886577543313),Asia(0.000235963540262122),Europe(0.000300277574647508),NorthAmerica(0.000177067512600473),Oceania(0.0000716503463100072),SouthAmerica(0.000021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a2f&&LOCATION=1:23032:T:G
23030T>C 1 23030 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F490L None - None 0.65 Tolerated -3.3 -0.987717 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0002560148686 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations at positions E484, F490, Q493, and S494 conferred complete or partial resistance to C121 and C144 Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.00131886577543313),Asia(0.000235963540262122),Europe(0.000300277574647508),NorthAmerica(0.000177067512600473),Oceania(0.0000716503463100072),SouthAmerica(0.000021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a26&&LOCATION=1:23030:T:C
24224T>C 1 24224 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F888L B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.001956857436 Experimental Structural modelling of Spike protein Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ Africa(0.0196630897428212),Asia(0.00129442856372364),Europe(0.00172275153001946),NorthAmerica(0.00204126421216179),Oceania(0.000453785526630045),SouthAmerica(0.000021095933758768)
24224T>C 1 24224 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 F888L B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.001956857436 Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report##High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.0196630897428212),Asia(0.00129442856372364),Europe(0.00172275153001946),NorthAmerica(0.00204126421216179),Oceania(0.000453785526630045),SouthAmerica(0.000021095933758768)
23016G>A 1 23016 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 G485D None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.00001425961136 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Europe(0.00000242812054971031),NorthAmerica(0.0000367851522655913) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
23118A>C 1 23118 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 H519P None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000003510058181 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.####Neutralization assays with monoclonal antibodies were also performed. Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Africa(0.0000199828147792898),Asia(0.0000101127231540909),Europe(0.0000016187470331402),NorthAmerica(0.00000436434009930744),SouthAmerica(0.000010547966879384)
23118A>C 1 23118 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 H519P None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000003510058181 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR.####Neutralization assays with monoclonal antibodies were also performed. Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000199828147792898),Asia(0.0000101127231540909),Europe(0.0000016187470331402),NorthAmerica(0.00000436434009930744),SouthAmerica(0.000010547966879384) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85b41&&LOCATION=1:23118:A:C
23525C>T 1 23525 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 H655Y P.1##B.1.616 https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.616 Characteristic mutation of P.1 and B.1.616 lineages 0.02312557957 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.0108306856103751),Asia(0.00193153012243137),Europe(0.00616864025653903),NorthAmerica(0.0302748037917387),Oceania(0.000883687604490088),SouthAmerica(0.426781287906756) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22863T>A 1 22863 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 I434K None - None 0.05 Deleterious 1.65 2.13354 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA NA S Reverse NA NA NA No co - mutations reported NA 0.0000008775145454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000199828147792898),Asia(0.00000337090771803031),Europe(0.000000809373516570102) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8583f&&LOCATION=1:22863:T:A
22964A>T 1 22964 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 I468F None - None 0.35 Tolerated -3.3 0.0110866 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_LKPFERDISTEIYQA 14 Surface glycoprotein_KPFERDISTEI -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000005265087272 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Changes in RBD region demonstrates altered sensitivity to neutralizing mAbs. I468F was observed to be more susceptible to neutralization mediated by mAbs. Also, this variation is found to possess increased sensitivity to the convalescent sera compared with reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.0000101127231540909),Europe(0.00000445155434113556),NorthAmerica(0.00000498781725635136),Oceania(0.0000477668975400048) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8595f&&LOCATION=1:22964:A:T
22965T>C 1 22965 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 I468T None - None 0.2 Tolerated 1.65 2.13354 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_LKPFERDISTEIYQA 14 Surface glycoprotein_KPFERDISTEI -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00001711153363 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Changes in RBD region demonstrates altered sensitivity to neutralizing mAbs. I468T was observed to be more susceptible to neutralization mediated by mAbs. Also, this variation is found to possess increased sensitivity to the convalescent sera compared with reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000999140738964491),Asia(0.0000202254463081819),Europe(0.0000109265424736964),NorthAmerica(0.0000224451776535811),Oceania(0.0000477668975400048),SouthAmerica(0.000021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85961&&LOCATION=1:22965:T:C
22695A>G 1 22695 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K378R None - None 0.13 Tolerated 1.65 2.25839 0.0472441 NA BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NSASFSTFK 0.08 NA NA NA NA NA NA NA No co - mutations reported NA 0.000007897630908 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000199828147792898),Asia(0.0000134836308721212),Europe(0.00000607030137427576),NorthAmerica(0.0000093521573556588),SouthAmerica(0.000010547966879384) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8566e&&LOCATION=1:22695:A:G
22811A>G 1 22811 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K417E None - None 0.26 Tolerated 0.737 2.63294 1 disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_RQIAPGQTGK 0.03 NA NA nCoV-2019_76_LEFT NA NA NA NA No co - mutations reported NA 0.000006361980454 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000199828147792898),Asia(0.00000337090771803031),Europe(0.00000445155434113556),NorthAmerica(0.00000997563451270272) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef857ad&&LOCATION=1:22811:A:G
22812A>C 1 22812 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K417T P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1 lineage 0.02047965384 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.0000599484443378694),Asia(0.000677552451324093),Europe(0.00420024386424054),NorthAmerica(0.0285982737164476),Oceania(0.000358251731550036),SouthAmerica(0.389072306312958) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22894G>T 1 22894 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K444N None - None 0.54 Tolerated 0.498 -7.72964 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.00014961623 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay.The K444N and V445E mutants retained near Wild Type (WT) levels of binding to all three antibodies, despite exhibiting partial resistance to C135 Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.000119896888675739),Asia(0.000114610862413031),Europe(0.000123024774518655),NorthAmerica(0.000182678807013869),Oceania(0.0000477668975400048),SouthAmerica(0.000453562575813512) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85893&&LOCATION=1:22894:G:T
22892A>G 1 22892 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K444Q None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0000004387572727 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous NorthAmerica(0.00000124695431408784) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22936G>C 1 22936 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K458N None - None 0.43 Tolerated -3.3 -6.85569 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_RLFRKSNLK 0.01 NA NA NA NA NA NA NA No co - mutations reported NA 0.00005879347454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000399656295585796),Asia(0.0000640472466425759),Europe(0.0000764857973158746),NorthAmerica(0.000031173857852196),Oceania(0.0000238834487700024),SouthAmerica(0.000073835768155688) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8590e&&LOCATION=1:22936:G:C
22936G>T 1 22936 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K458N None - None 0.43 Tolerated -3.3 -6.85569 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_RLFRKSNLK 0.01 NA NA NA NA NA NA NA No co - mutations reported NA 0.00005879347454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000399656295585796),Asia(0.0000640472466425759),Europe(0.0000764857973158746),NorthAmerica(0.000031173857852196),Oceania(0.0000238834487700024),SouthAmerica(0.000073835768155688) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8590f&&LOCATION=1:22936:G:T
22935A>G 1 22935 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K458R None - None 0.51 Tolerated -3.3 -2.11137 0 disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_RLFRKSNLK 0.01 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.00002478978591 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A).##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies##The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000599484443378694),Asia(0.0000235963540262122),Europe(0.0000121406027485515),NorthAmerica(0.0000436434009930744),SouthAmerica(0.000031643900638152) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8590b&&LOCATION=1:22935:A:G
22935A>G 1 22935 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K458R None - None 0.51 Tolerated -3.3 -2.11137 0 disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_RLFRKSNLK 0.01 NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.00002478978591 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants.##pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A).##Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ Africa(0.0000599484443378694),Asia(0.0000235963540262122),Europe(0.0000121406027485515),NorthAmerica(0.0000436434009930744),SouthAmerica(0.000031643900638152)
21614C>T 1 21614 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L18F P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1 lineage 0.04316406297 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.101812441300482),Asia(0.00887560002157381),Europe(0.0379373601554321),NorthAmerica(0.0354621337383441),Oceania(0.00217339383807022),SouthAmerica(0.404134803016719) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22917T>G 1 22917 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L452R B.1.427/B.1.429## B.1.617.1## B.1.617.2## B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.427##https://outbreak.info/situation-reports?pango=B.1.617.1##https://outbreak.info/situation-reports?pango=B.1.617.2##https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.427/B.1.429, B.1.617.1, B.1.617.2 and B.1.617.3 lineages. 0.35 Tolerated -3.3 -1.23742 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.4606155019 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Africa(0.323142097795896),Asia(0.38367671646621),Europe(0.461651275754771),NorthAmerica(0.493993421069039),Oceania(0.446859326486745),SouthAmerica(0.188323400664522)
21575C>T 1 21575 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L5F None - None 0.05 Deleterious -3.25 -7.36907 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA homoplasic position NA Signal peptide mutation. Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.0271239746 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Foley, B., Giorgi, E. E., Bhattacharya, T., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., LaBranche, C. C., Montefiori, D. C., & on behalf of the Sheffield COVID-19 Genomics Group. (n.d.). Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. https://doi.org/10.1101/2020.04.29.069054 https://www.sciencedirect.com/science/article/pii/S0092867420308205?via%3Dihub Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 B Korber, WM Fischer, S Gnanakaran, H Yoon, J Theiler, W Abfalterer, B Foley, EE Giorgi, T Bhattacharya, MD Parker, DG Partridge, CM Evans, TM Freeman, TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group, CC LaBranche, DC Montefiori##Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.011170393461623),Asia(0.0343057278463945),Europe(0.0161336469925501),NorthAmerica(0.0445087872870514),Oceania(0.00355863386673036),SouthAmerica(0.015821950319076) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef848d8&&LOCATION=1:21575:C:T
21575C>T 1 21575 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L5F None - None 0.05 Deleterious -3.25 -7.36907 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA homoplasic position NA Signal peptide mutation. Functional consequences induced by co - occurring mutations Co-occuring with 23403A>G (D614G) 0.0271239746 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Africa(0.011170393461623),Asia(0.0343057278463945),Europe(0.0161336469925501),NorthAmerica(0.0445087872870514),Oceania(0.00355863386673036),SouthAmerica(0.015821950319076)
21584T>G 1 21584 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 L8V None - None 0.83 Tolerated -3.25 -0.0874331 0 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA signal peptide mutation NA 0.00007612438681 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Signal peptide mutation Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Foley, B., Giorgi, E. E., Bhattacharya, T., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., LaBranche, C. C., Montefiori, D. C., & on behalf of the Sheffield COVID-19 Genomics Group. (n.d.). Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. https://doi.org/10.1101/2020.04.29.069054 https://www.sciencedirect.com/science/article/pii/S0092867420308205?via%3Dihub Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 B Korber, WM Fischer, S Gnanakaran, H Yoon, J Theiler, W Abfalterer, B Foley, EE Giorgi, T Bhattacharya, MD Parker, DG Partridge, CM Evans, TM Freeman, TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group, CC LaBranche, DC Montefiori Asia(0.000242705355698182),Europe(0.000102790436604403),NorthAmerica(0.0000130930202979223) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef848f3&&LOCATION=1:21584:T:G
25273G>C 1 25273 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 M1237I None - None 0.05 Deleterious -0.274 1.80496 1 NA NA NA NA Surface glycoprotein_MVTIMLCCMTS NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 25273G>C/T 0.001658063733 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00269767999520412),Asia(0.00136184671808425),Europe(0.00196232609092421),NorthAmerica(0.00119645266436728),Oceania(0.000979221399570098),SouthAmerica(0.00221507304467064) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54b06dcd0a2abef873de&&LOCATION=1:25273:G:C
25273G>T 1 25273 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 M1237I None - None 0.05 Deleterious -0.274 1.80496 1 NA NA NA NA Surface glycoprotein_MVTIMLCCMTS NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 25273G>C/T 0.001658063733 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00269767999520412),Asia(0.00136184671808425),Europe(0.00196232609092421),NorthAmerica(0.00119645266436728),Oceania(0.000979221399570098),SouthAmerica(0.00221507304467064) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54b06dcd0a2abef873de&&LOCATION=1:25273:G:C
22007A>C 1 22007 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N149H None - None 0.24 Tolerated -3.3 0.040315 0 Disulf_bond BetaCoV_S1-NTD glyco NA Surface glycoprotein_HKNNKSWMESEFRVYSSANNCTF NA NA Surface glycoprotein_GVYYHKNNK 0.03 NA NA NA NA NA NA NA No co - mutations reported NA 0.000001974407727 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was accessed. Increased sensitivity to convalescent sera. This mutation was found to possess over 4-fold sensitivity to one or two of the ten tested sera. Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.00000337090771803031),Europe(0.00000202343379142525),NorthAmerica(0.00000187043147113176) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef84df9&&LOCATION=1:22007:A:C
22622A>G 1 22622 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N354D None - None 0.04 Deleterious 0.737 2.63294 0.992126 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.00008226698863 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was accessed. Increased sensitivity to convalescent sera. This mutation was found to possess over 4-fold sensitivity to one or two of the ten tested sera.##This mutation resulted in no observed neutralization with hIgG1 isotype control. Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Africa(0.0000199828147792898),Asia(0.0000505636157704547),Europe(0.000110479485011819),NorthAmerica(0.0000411494923648987),SouthAmerica(0.00021095933758768)
22622A>G 1 22622 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N354D None - None 0.04 Deleterious 0.737 2.63294 0.992126 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.00008226698863 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was accessed. Increased sensitivity to convalescent sera. This mutation was found to possess over 4-fold sensitivity to one or two of the ten tested sera.##This mutation resulted in no observed neutralization with hIgG1 isotype control. Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000199828147792898),Asia(0.0000505636157704547),Europe(0.000110479485011819),NorthAmerica(0.0000411494923648987),SouthAmerica(0.00021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef855a7&&LOCATION=1:22622:A:G
22882T>G 1 22882 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N440K None - None 0.73 Tolerated -3.3 0.135937 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.001972433319 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Sensitivity of isolated RBD mutants to neutralization by the three monoclonal antibodies was determined. N440 mutants that emerged during replication in the presence of C135 were resistant to C135, but retained full sensitivity to both C121 and C144 antibodies. Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.00445616769578163),Asia(0.0115352462110997),Europe(0.000633334776716105),NorthAmerica(0.00218404048112485),Oceania(0.000310484834010031),SouthAmerica(0.00279521122303676) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85873&&LOCATION=1:22882:T:G
22910A>G 1 22910 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N450D None - None 0.29 Tolerated -3.3 -0.613165 0 disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00001601464045 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.000159862518234318),Asia(0.0000134836308721212),Europe(0.0000153780968148319),NorthAmerica(0.0000118460659838345),SouthAmerica(0.000042191867517536) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858c2&&LOCATION=1:22910:A:G
23063A>G 1 23063 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N501Y B.1.1.7## B.1.351## P.1##P.3 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=P.3 Characteristic mutation of B.1.1.7, B.1.351, P.1 and P.3 lineages. 0.62 Tolerated -3.3 -0.613165 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.2844965776 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Residues in S1-2 region of RBD domain were identified as the key residues contributing to the binding to the host receptor ACE2. Antibodies targeting this region may block the virus binding to the host cell receptor and the subsequent membrane fusion between virus and host cell. Variations in N501 residue might potentially alter viral binding properties. N501Y, targets an AA predicted to have a strong role in the interaction.##Mutation N501Y is a key contact residue in the receptor binding domain and enhances virus binding affinity to human angiotensin-converting enzyme 2 Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Africa(0.278500489578962),Asia(0.242115446847527),Europe(0.338355765794823),NorthAmerica(0.204322193043491),Oceania(0.0219727728684022),SouthAmerica(0.488792785190655)
25350C>T 1 25350 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 P1263L None - None 1 Tolerated 1.65 3.2969 0.992126 NA NA NA NA NA NA NA Surface glycoprotein_SEPVLKGVKL -1 Spike glycoprotein CKFDEDDSEPVLKGVKLHYT nCoV-2019_83_RIGHT NA NA NA NA No co - mutations reported NA 0.001189690345 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This mutation was found to have significantly decreased infectivity in comparison to the reference strain. Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00111903762764023),Asia(0.00086632328353379),Europe(0.00135570064025492),NorthAmerica(0.000978235659401911),Oceania(0.00128970623358013),SouthAmerica(0.00144507146247561) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54b06dcd0a2abef874c3&&LOCATION=1:25350:C:T
21638C>T 1 21638 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 P26S P.1##B.1.620 https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of P.1 and B.1.620 lineages 0.02272806548 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.00343704414203785),Asia(0.00307089693112561),Europe(0.0057878300169928),NorthAmerica(0.0312667559485956),Oceania(0.00050155242417005),SouthAmerica(0.401318495859923) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
23034C>G 1 23034 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 P491R None - None 0.11 Tolerated 1.65 2.00869 0.0314961 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0000002193786363 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Oceania(0.0000238834487700024) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a35&&LOCATION=1:23034:C:G
23123C>T 1 23123 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 P521S None - None 1 Tolerated 1.65 3.2572 1 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA nCoV-2019_77_LEFT SARS-CoV-2_IBS_S1_F NA NA NA No co - mutations reported NA 0.00006230353272 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.000279759406910057),Asia(0.0000505636157704547),Europe(0.0000538233388519118),NorthAmerica(0.0000710763959030069),Oceania(0.0000716503463100072),SouthAmerica(0.00005273983439692) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85b58&&LOCATION=1:23123:C:T
24775A>C/T 1 24775 A C/T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q1071H B.1.617.1 https://outbreak.info/situation-reports?pango=B.1.617.1 Characteristic mutation of B.1.617.1 lineage 0 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 0
22277C>A 1 22277 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q239K None - None 0.34 Tolerated -3.3 0.040315 0 NA BetaCoV_S1-NTD NA NA NA Surface glycoprotein_IGINITRFQTLLALH 18 Surface glycoprotein_INITRFQTL 0.06 NA NA nCoV-2019_74_LEFT NA NA NA NA No co - mutations reported NA 0.00001469836863 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Durmaz, B., Abdulmajed, O., & Durmaz, R. ı. (2020). Mutations Observed in the SARS-CoV-2 Spike Glycoprotein and Their Effects in the Interaction of Virus with ACE-2 Receptor. Medeniyet Medical Journal, 1. https://doi.org/10.5222/mmj.2020.98048 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584268/ Mutations Observed in the SARS-CoV-2 Spike Glycoprotein and Their Effects in the Interaction of Virus with ACE-2 Receptor Africa(0.0000399656295585796),Asia(0.0000168545385901516),Europe(0.0000137593497816917),NorthAmerica(0.0000149634517690541),SouthAmerica(0.000021095933758768)
22277C>A 1 22277 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q239K None - None 0.34 Tolerated -3.3 0.040315 0 NA BetaCoV_S1-NTD NA NA NA Surface glycoprotein_IGINITRFQTLLALH 18 Surface glycoprotein_INITRFQTL 0.06 NA NA nCoV-2019_74_LEFT NA NA NA NA No co - mutations reported NA 0.00001469836863 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Bengül Durmaz, Olkar Abdulmajed, and Rıza Durmaz Africa(0.0000399656295585796),Asia(0.0000168545385901516),Europe(0.0000137593497816917),NorthAmerica(0.0000149634517690541),SouthAmerica(0.000021095933758768) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8510c&&LOCATION=1:22277:C:A
22787C>G 1 22787 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q321L None - None 0.25 Tolerated 1.65 3.2572 0.88189 disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_RQIAPGQTGK 0.03 NA NA NA NA NA NA NA Co - mutations reported Co-occuring with 23403A>G (D614G) 0.00006318104727 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.000239793777351478),Asia(0.0000370799848983334),Europe(0.0000602983269844726),NorthAmerica(0.0000673355329607434),SouthAmerica(0.000084383735035072) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85773&&LOCATION=1:22787:C:G
29498C>G 1 29498 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q409E None - None 0.16 Tolerated -2.21 -0.0880472 0.992126 NA NA NA NA Nucleocapsid phosphoprotein_KQLQQSMSSADS NA NA NA NA NA NA nCoV-2019_98_LEFT NA NA NA NA No co - mutations reported NA 0.0000004387572727 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Asia(0.00000337090771803031),Europe(0.000000404686758285051) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54b06dcd0a2abef8a66e&&LOCATION=1:29498:C:G
22802C>G 1 22802 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q414E None - None 0.95 Tolerated -3.3 -1.48712 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_RQIAPGQTGK 0.03 NA NA nCoV-2019_76_LEFT NA NA NA NA No co - mutations reported NA 0.000000658135909 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.00000337090771803031),NorthAmerica(0.00000124695431408784) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85797&&LOCATION=1:22802:C:G
22803A>C 1 22803 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q414P None - None 0.22 Tolerated 1.65 2.25839 0.00787402 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_RQIAPGQTGK 0.03 NA NA nCoV-2019_76_LEFT NA NA NA NA No co - mutations reported NA 0.000001974407727 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.0000101127231540909),Europe(0.000000404686758285051),NorthAmerica(0.0000031173857852196) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8579a&&LOCATION=1:22803:A:C
23039C>A 1 23039 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q493K None - None 0.47 Tolerated -3.3 -2.11137 0 disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00003290679545 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000399656295585796),Asia(0.0000101127231540909),Europe(0.0000356124347290845),NorthAmerica(0.0000355381979515035) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a45&&LOCATION=1:23039:C:A
21717A>G 1 21717 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q52R B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.001841025516 Experimental Structural modelling of Spike protein Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ Africa(0.0203225226305377),Asia(0.00118318860902864),Europe(0.00147427386043244),NorthAmerica(0.00209862411060984),Oceania(0.000214951038930022),SouthAmerica(0.000063287801276304)
21717A>G 1 21717 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q52R B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage 0.001841025516 Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report##High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.0203225226305377),Asia(0.00118318860902864),Europe(0.00147427386043244),NorthAmerica(0.00209862411060984),Oceania(0.000214951038930022),SouthAmerica(0.000063287801276304)
23587G>C 1 23587 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q675H None - None 0.31 Tolerated -3.09 -0.454362 0.944882 NA NA NA NA Surface glycoprotein_SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIA NA NA NA NA Spike glycoprotein DIPIGAGICASYHTVSLL NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 23587G>C/T 0.006371633114 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00583498191555263),Asia(0.0152263901623429),Europe(0.00216386009655017),NorthAmerica(0.0108104704259845),Oceania(0.000859804155720086),SouthAmerica(0.015959073888508) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef860e5&&LOCATION=1:23587:G:C
23587G>T 1 23587 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q675H None - None 0.31 Tolerated -3.09 -0.454362 0.944882 NA NA NA NA Surface glycoprotein_SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIA NA NA NA NA Spike glycoprotein DIPIGAGICASYHTVSLL NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 23587G>C/T 0.006371633114 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.00583498191555263),Asia(0.0152263901623429),Europe(0.00216386009655017),NorthAmerica(0.0108104704259845),Oceania(0.000859804155720086),SouthAmerica(0.015959073888508) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef860e8&&LOCATION=1:23587:G:T
23593G>C 1 23593 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q677H B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage. 0.11 Tolerated -3.09 -1.33071 0 NA Surface glycoprotein_SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIA NA NA NA Spike glycoprotein_DIPIGAGICASYHTVSLL NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0110933195 Experimental Structural modelling of Spike protein Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ Africa(0.0354495134184601),Asia(0.0108678064829297),Europe(0.00883350255984609),NorthAmerica(0.0138854597645251),Oceania(0.00224504418438022),SouthAmerica(0.0145140024260324)
23593G>T 1 23593 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q677H B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage. 0.11 Tolerated -3.09 -1.33071 0 NA Surface glycoprotein_SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIA NA NA NA Spike glycoprotein_DIPIGAGICASYHTVSLL NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0110933195 Experimental Structural modelling of Spike protein Ozer, E. A., Simons, L. M., Adewumi, O. M., Fowotade, A. A., Omoruyi, E. C., Adeniji, J. A., Dean, T. J., Taiwo, B. O., Hultquist, J. F., & Lorenzo-Redondo, R. (2021). High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria. medRxiv : the preprint server for health sciences, 2021.04.09.21255206. https://doi.org/10.1101/2021.04.09.21255206 https://pubmed.ncbi.nlm.nih.gov/33880483/ Africa(0.0354495134184601),Asia(0.0108678064829297),Europe(0.00883350255984609),NorthAmerica(0.0138854597645251),Oceania(0.00224504418438022),SouthAmerica(0.0145140024260324)
23593G>C 1 23593 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q677H B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage. 0.11 Tolerated -3.09 -1.33071 0 NA Surface glycoprotein_SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIA NA NA NA Spike glycoprotein_DIPIGAGICASYHTVSLL NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0110933195 Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Africa(0.0354495134184601),Asia(0.0108678064829297),Europe(0.00883350255984609),NorthAmerica(0.0138854597645251),Oceania(0.00224504418438022),SouthAmerica(0.0145140024260324)
23593G>T 1 23593 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Q677H B.1.525 https://outbreak.info/situation-reports?pango=B.1.525 Characteristic mutation of B.1.525 lineage. 0.11 Tolerated -3.09 -1.33071 0 NA Surface glycoprotein_SYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIA NA NA NA Spike glycoprotein_DIPIGAGICASYHTVSLL NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0110933195 Experimental Structural modelling of Spike protein Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 https://pubmed.ncbi.nlm.nih.gov/33990970/ Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report##High prevalence of SARS-CoV-2 B.1.1.7 (UK variant) and the novel B.1.5.2.5 lineage in Oyo State, Nigeria Felicidade Pereira 1, Stephane Tosta 1 2, Maricélia Maia Lima 3, Luciana Reboredo de Oliveira da Silva 1, Vanessa Brandão Nardy 1, Marcela Kelly Astete Gómez 1, Jaqueline Gomes Lima 1, Vagner Fonseca 2 4 5, Tulio de Oliveira 5, Jose Lourenço 6, Luiz Carlos Junior Alcantara 2 7, Marta Giovanetti 2 7, Arabela Leal 1##Egon A Ozer, Lacy M Simons, Olubusuyi M Adewumi, Adeola A Fowotade, Ewean C Omoruyi, Johnson A Adeniji, Taylor J Dean, Babafemi O Taiwo, Judd F Hultquist, Ramon Lorenzo-Redondo Africa(0.0354495134184601),Asia(0.0108678064829297),Europe(0.00883350255984609),NorthAmerica(0.0138854597645251),Oceania(0.00224504418438022),SouthAmerica(0.0145140024260324)
22132G>T 1 22132 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R190S P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1 lineage 0.01989698418 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.00557520532342186),Asia(0.000704519713068335),Europe(0.00407762377648017),NorthAmerica(0.0268756063315352),Oceania(0.000477668975400048),SouthAmerica(0.390348610305364) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22599G>A 1 22599 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R346K None - None 0.75 Tolerated -3.3 -0.738016 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 Surface glycoprotein_GEVFNATRF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.002896456136 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Sensitivity of isolated RBD mutants to neutralization by the three monoclonal antibodies was determined. R346 mutants that emerged during replication in the presence of C135 were resistant to C135, but retained full sensitivity to both C121 and C144 antibodies. Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.000379673480806506),Asia(0.000185399924491667),Europe(0.000607434824185861),NorthAmerica(0.00412180748521736),Oceania(0.0000238834487700024),SouthAmerica(0.0529086018669901) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85562&&LOCATION=1:22599:G:A
22599G>N/A 1 22599 G NA S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R346L None - None NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0000004387572727 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Sensitivity of isolated RBD mutants to neutralization by the three monoclonal antibodies was determined. R346 mutants that emerged during replication in the presence of C135 were resistant to C135, but retained full sensitivity to both C121 and C144 antibodies. Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Europe(0.000000809373516570102) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22600A>C 1 22600 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R346S None - None 1 Tolerated -3.3 -5.23263 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 Surface glycoprotein_GEVFNATRF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0005330900863 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Sensitivity of isolated RBD mutants to neutralization by the three monoclonal antibodies was determined. R346S mutants that emerged during replication in the presence of C135 were resistant to C135, but retained full sensitivity to both C121 and C144 antibodies. Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.00225805807005975),Asia(0.00021236718623591),Europe(0.000711844007823405),NorthAmerica(0.000284929060769072),Oceania(0.000406018629090041),SouthAmerica(0.000221507304467064) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22600A>T 1 22600 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R346S None - None 1 Tolerated -3.3 -5.23263 0 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 Surface glycoprotein_GEVFNATRF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0005330900863 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Sensitivity of isolated RBD mutants to neutralization by the three monoclonal antibodies was determined. R346S mutants that emerged during replication in the presence of C135 were resistant to C135, but retained full sensitivity to both C121 and C144 antibodies. Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.00225805807005975),Asia(0.00021236718623591),Europe(0.000711844007823405),NorthAmerica(0.000284929060769072),Oceania(0.000406018629090041),SouthAmerica(0.000221507304467064) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
23088G>A 1 23088 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 R509K None - None 0.46 Tolerated 1.65 4.256 0.448819 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_QPYRVVVLSFELLHA 14 Surface glycoprotein_QPYRVVVL -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000002413165 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.0000101127231540909),Europe(0.00000202343379142525),NorthAmerica(0.00000124695431408784) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85ae1&&LOCATION=1:23088:G:A
22303T>G 1 22303 T G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S359N None - None 0.06 Tolerated -3.16 -0.215181 0.00787402 NA BetaCoV_S1-NTD NA NA NA Surface glycoprotein_TRFQTLLALHRSYLT 9.2 Surface glycoprotein_LLALHRSYL 0.14 NA NA NA NA NA NA NA No co - mutations reported NA 0.00007327246454 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000399656295585796),Asia(0.0000505636157704547),Europe(0.0000489670977524912),NorthAmerica(0.000122201522780608) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85160&&LOCATION=1:22303:T:G
22875C>T 1 22875 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S438F None - None 0.06 Tolerated 1.65 3.2572 0.614173 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_IAWNSNNLDSK NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.000001096893182 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Europe(0.0000016187470331402),NorthAmerica(0.00000062347715704392) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85861&&LOCATION=1:22875:C:T
23042T>C 1 23042 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S494P None - None 0.23 Tolerated -3.3 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA Surface glycoprotein_YFPLQSYGF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.002792031905 Experimental This study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis. Mutations in proximity to ACE binding site and neutralizing epitopes were tested for their ability to confer resistance to the monoclonal antibodies, using an HIV-1-based pseudotyped virus-based assay. Naturally occurring mutations at positions E484, F490, Q493, and S494 conferred complete or partial resistance to C121 and C144 Weisblum, Y., Schmidt, F., Zhang, F., DaSilva, J., Poston, D., Lorenzi, J. C. C., Muecksch, F., Rutkowska, M., Hoffmann, H.-H., Michailidis, E., Gaebler, C., Agudelo, M., Cho, A., Wang, Z., Gazumyan, A., Cipolla, M., Luchsinger, L., Hillyer, C. D., Caskey, M., … Bieniasz, P. D. (2020). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. ELife, 9, 1. https://doi.org/10.7554/elife.61312 https://pubmed.ncbi.nlm.nih.gov/33112236/ Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz Africa(0.000899226665068042),Asia(0.000626988835553638),Europe(0.00134882096536407),NorthAmerica(0.00563810393114817),Oceania(0.000310484834010031),SouthAmerica(0.00112863245609409) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85a4f&&LOCATION=1:23042:T:C
24390G>C 1 24390 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 S943T None - None 0.57 Tolerated 0.475 1.00989 0 disulf_bond NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA Functional consequences induced by co - occurring mutations 23403A>G ; 24390G>C 0.00005594155227 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.000199828147792898),Asia(0.000482039803678335),Europe(0.0000105218557154113),NorthAmerica(0.0000386555837367231),SouthAmerica(0.000147671536311376) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef86a12&&LOCATION=1:24390:G:C
21600GTCAGTGTGTTAATCTTACAACCAGAAC>G 1 21600 GTCAGTGTGTTAATCTTACAACCAGAAC G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 SΔCT13 - cytoplasmic tail deletion of 13 amino acids 0 Experimental Sequences of full-length spike (S) or 13 amino acids in cytoplasmic tail deleted S (SΔCT) of SARS-CoV-1 and SARS-CoV-2 were codon optimized and commercially synthesized. Synthetic genes were cloned into the mammalian expression plasmid pcDNA3.1+. SARS-CoV-2 S D614G and V367F variants were generated by site-directed mutagenesis based on SARS-CoV-2 SΔCT. Human ACE2 genes were commercially synthesized and further cloned into pQCXIP retroviral vector. SΔCT13, conferred enhanced spike incorporation into pseudovirions and increased viral entry into cells compared to that with full-length spike (S) Yu, J., Li, Z., He, X., Gebre, M. S., Bondzie, E. A., Wan, H., Jacob-Dolan, C., Martinez, D. R., Nkolola, J. P., Baric, R. S., & Barouch, D. H. (2021). Deletion of the SARS-CoV-2 Spike Cytoplasmic Tail Increases Infectivity in Pseudovirus Neutralization Assays. Journal of virology, JVI.00044-21. Advance online publication. https://doi.org/10.1128/JVI.00044-21 https://pubmed.ncbi.nlm.nih.gov/33727331/ Deletion of the SARS-CoV-2 Spike Cytoplasmic Tail Increases Infectivity in Pseudovirus Neutralization Assays Jingyou Yu, Zhenfeng Li, Xuan He, Makda S Gebre, Esther A Bondzie, Huahua Wan, Catherine Jacob-Dolan, David R Martinez, Joseph P Nkolola, Ralph S Baric, Dan H Barouch 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
24642C>T 1 24642 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T1027I P.1##B.1.620 https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of P.1 and B.1.620 lineages 0.02299439115 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.00463601302879524),Asia(0.00947899250310124),Europe(0.00544586970624193),NorthAmerica(0.0308708479538727),Oceania(0.0010269882971101),SouthAmerica(0.408818100311165) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
21618C>G 1 21618 C G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T19R B.1.617.2##B.1.617.3 https://outbreak.info/situation-reports?pango=B.1.617.2##https://outbreak.info/situation-reports?pango=B.1.617.3 Characteristic mutation of B.1.617.2 and B.1.617.3 lineages 0.4457315389 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 Africa(0.310433027596267),Asia(0.363623186451648),Europe(0.464190280476252),NorthAmerica(0.452018444948214),Oceania(0.452137568664915),SouthAmerica(0.183766678972628)
21621C>A 1 21621 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T20N P.1 https://outbreak.info/situation-reports?pango=P.1 Characteristic mutation of P.1 lineage 0.02038115283 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.000119896888675739),Asia(0.000873065098969851),Europe(0.00414803927242177),NorthAmerica(0.0278120690214152),Oceania(0.000358251731550036),SouthAmerica(0.398354517166816) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22995C>T 1 22995 C T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T478I None - None 0.17 Tolerated -2.14 -1.73682 0 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_STEIYQAGSTPCNGV NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0001998539377 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera. This mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.000159862518234318),Asia(0.000353945310393183),Europe(0.000233099572772189),NorthAmerica(0.000130306725822179),SouthAmerica(0.000137123569431992) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef859c5&&LOCATION=1:22995:C:T
22995C>A 1 22995 C A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T478K B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.2 lineage 0.4459300766 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 Pereira, F., Tosta, S., Lima, M. M., Reboredo de Oliveira da Silva, L., Nardy, V. B., Gómez, M., Lima, J. G., Fonseca, V., de Oliveira, T., Lourenço, J., Alcantara, L., Giovanetti, M., & Leal, A. (2021). Genomic surveillance activities unveil the introduction of the SARS-CoV-2 B.1.525 variant of interest in Brazil: Case Report. Journal of medical virology, 10.1002/jmv.27086. Advance online publication. https://doi.org/10.1002/jmv.27086 Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 Africa(0.314129848330436),Asia(0.363458011973464),Europe(0.458930161992063),NorthAmerica(0.460996516009646),Oceania(0.440888464294244),SouthAmerica(0.182057908338168)
23717A>G 1 23717 A G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 T719A None - None 0.01 Deleterious -1.04 0.860157 1 NA NA NA NA Surface glycoprotein_TISVTTEILPVSMTKTSVDCT NA NA Surface glycoprotein_IPTNFTISV 0.11 NA NA NA NA NA NA NA No co - mutations reported NA 0.000003948815454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.00000674181543606062),Europe(0.00000364218082456546),NorthAmerica(0.00000436434009930744) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef8626d&&LOCATION=1:23717:A:G
25088G>T 1 25088 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V1176F P.1##P.3 https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=P.3 Characteristic mutation of P.1 and P.3 lineages 0.02391556204 Experimental Study includes generation of various Plasmid constructs, HEK-293T cells and derivatives were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37oC and 5% CO2, Replication competent VSV/SARS-CoV-2/GFP chimeric virus and HIV-1/CCNanoLuc2AEGFP-SARS-CoV-2 pseudotype particles. Selection of viruses in the presence of antibodies was followed by sequence anlysis.####Neutralization assays with monoclonal antibodies were also performed. Dejnirattisai, W., Zhou, D., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H., Tuekprakhon, A., Nutalai, R., Wang, B., López-Camacho, C., Slon-Campos, J., Walter, T. S., Skelly, D., Costa Clemens, S. A., Naveca, F. G., Nascimento, V., Nascimento, F., Fernandes da Costa, C., … Screaton, G. R. (2021). Antibody evasion by the P.1 strain of SARS-CoV-2. Cell, S0092-8674(21)00428-1. Advance online publication. https://doi.org/10.1016/j.cell.2021.03.055 https://pubmed.ncbi.nlm.nih.gov/33852911/ Antibody evasion by the P.1 strain of SARS-CoV-2 Wanwisa Dejnirattisai 1, Daming Zhou 2, Piyada Supasa 3, Chang Liu 4, Alexander J Mentzer 5, Helen M Ginn 6, Yuguang Zhao 2, Helen M E Duyvesteyn 2, Aekkachai Tuekprakhon 3, Rungtiwa Nutalai 3, Beibei Wang 3, César López-Camacho 3, Jose Slon-Campos 3, Thomas S Walter 2, Donal Skelly 7, Sue Ann Costa Clemens 8, Felipe Gomes Naveca 9, Valdinete Nascimento 9, Fernanda Nascimento 9, Cristiano Fernandes da Costa 10, Paola Cristina Resende 11, Alex Pauvolid-Correa 12, Marilda M Siqueira 11, Christina Dold 13, Robert Levin 14, Tao Dong 15, Andrew J Pollard 13, Julian C Knight 16, Derrick Crook 17, Teresa Lambe 18, Elizabeth Clutterbuck 13, Sagida Bibi 13, Amy Flaxman 18, Mustapha Bittaye 18, Sandra Belij-Rammerstorfer 18, Sarah C Gilbert 18, Miles W Carroll 19, Paul Klenerman 20, Eleanor Barnes 20, Susanna J Dunachie 21, Neil G Paterson 6, Mark A Williams 6, David R Hall 6, Ruben J G Hulswit 2, Thomas A Bowden 2, Elizabeth E Fry 2, Juthathip Mongkolsapaya 22, Jingshan Ren 23, David I Stuart 24, Gavin R Screaton 25##Nuno R Faria # 1 2 3 4, Thomas A Mellan # 5 2, Charles Whittaker # 5 2, Ingra M Claro # 3 6, Darlan da S Candido # 3 4, Swapnil Mishra # 5 2, Myuki A E Crispim 7 8, Flavia C S Sales 3 6, Iwona Hawryluk 5 2, John T McCrone 9, Ruben J G Hulswit 10, Lucas A M Franco 3 6, Mariana S Ramundo 3 6, Jaqueline G de Jesus 3 6, Pamela S Andrade 11, Thais M Coletti 3 6, Giulia M Ferreira 12, Camila A M Silva 3 6, Erika R Manuli 3 6, Rafael H M Pereira 13, Pedro S Peixoto 14, Moritz U G Kraemer 4, Nelson Gaburo Jr 15, Cecilia da C Camilo 15, Henrique Hoeltgebaum 16, William M Souza 17, Esmenia C Rocha 3 6, Leandro M de Souza 3 6, Mariana C de Pinho 3 6, Leonardo J T Araujo 18, Frederico S V Malta 19, Aline B de Lima 19, Joice do P Silva 19, Danielle A G Zauli 19, Alessandro C de S Ferreira 19, Ricardo P Schnekenberg 20, Daniel J Laydon 5 2, Patrick G T Walker 5 2, Hannah M Schlüter 16, Ana L P Dos Santos 21, Maria S Vidal 21, Valentina S Del Caro 21, Rosinaldo M F Filho 21, Helem M Dos Santos 21, Renato S Aguiar 22, José L Proença-Modena 23, Bruce Nelson 24, James A Hay 25 26, Mélodie Monod 16, Xenia Miscouridou 16, Helen Coupland 5 2, Raphael Sonabend 5 2, Michaela Vollmer 5 2, Axel Gandy 16, Carlos A Prete Jr 27, Vitor H Nascimento 27, Marc A Suchard 28, Thomas A Bowden 10, Sergei L K Pond 29, Chieh-Hsi Wu 30, Oliver Ratmann 16, Neil M Ferguson 5 2, Christopher Dye 4, Nick J Loman 31, Philippe Lemey 32, Andrew Rambaut 9, Nelson A Fraiji 7 33, Maria do P S S Carvalho 7 34, Oliver G Pybus # 4 35, Seth Flaxman # 16, Samir Bhatt # 1 2 36, Ester C Sabino # 37 6##Pengfei Wang 1, Ryan G Casner 2, Manoj S Nair 3, Maple Wang 3, Jian Yu 3, Gabriele Cerutti 2, Lihong Liu 3, Peter D Kwong 4, Yaoxing Huang 3, Lawrence Shapiro 5, David D Ho 6##Camila Malta Romano 1 2, Alvina Clara Felix 2, Anderson Vicente de Paula 2, Jaqueline Góes de Jesus 2, Pamela S Andrade 2, Darlan Cândido 2 3, Franciane M de Oliveira 2, Andreia C Ribeiro 4, Francini C da Silva 4, Marta Inemami 4, Angela Aparecida Costa 4, Cibele O D Leal 2, Walter Manso Figueiredo 4, Claudio Sergio Pannuti 2, William M de Souza 5, Nuno Rodrigues Faria 6 7, Ester Cerdeira Sabino 2 6##Isadora Cristina de Siqueira 1, Aquiles Assunção Camelier 2, Elves A P Maciel 3, Carolina Kymie Vasques Nonaka 4, Margarida Celia L C Neves 5, Yasmin Santos Freitas Macêdo 6, Karoline Almeida Félix de Sousa 6, Victor Costa Araujo 7, Aurea Angelica Paste 5, Bruno Solano de Freitas Souza 8, Tiago Gräf 6 Africa(0.00181843614491537),Asia(0.00444285637236395),Europe(0.00508367505757681),NorthAmerica(0.0311439309486579),Oceania(0.00114640554096011),SouthAmerica(0.475122620114973) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22583G>A 1 22583 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V341I None - None 0.39 Tolerated 0.738 1.88384 0.929134 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 Surface glycoprotein_GEVFNATRF -1 Spike glycoprotein VRFPNITNLCPFGEVFN NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occurrinng with 23403A>G (D614G) 0.00003488120318 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR. Also, neutralization assays were performed across SARS-CoV-2 spike RBD variants. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain.## This mutation resulted in no observed neutralization with hIgG1 isotype control. Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Africa(0.0000199828147792898),Asia(0.0000707890620786365),Europe(0.0000331843141793742),NorthAmerica(0.0000299269035381082),Oceania(0.0000716503463100072),SouthAmerica(0.000042191867517536)
22583G>A 1 22583 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V341I None - None 0.39 Tolerated 0.738 1.88384 0.929134 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_VFNATRFASVYAWNR 9.3 Surface glycoprotein_GEVFNATRF -1 Spike glycoprotein VRFPNITNLCPFGEVFN NA NA NA NA NA Functional consequences induced by co - occurring mutations Co-occurrinng with 23403A>G (D614G) 0.00003488120318 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR. Also, neutralization assays were performed across SARS-CoV-2 spike RBD variants. Eight anti-spike antibodies were tested against sixteen SARS-CoV-2 spike protein RBD variants. Variants were encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly increased infectivity in comparison to the reference strain.## This mutation resulted in no observed neutralization with hIgG1 isotype control. Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang##Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000199828147792898),Asia(0.0000707890620786365),Europe(0.0000331843141793742),NorthAmerica(0.0000299269035381082),Oceania(0.0000716503463100072),SouthAmerica(0.000042191867517536) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85531&&LOCATION=1:22583:G:A
22896T>C 1 22896 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V445A None - None 0.5 Tolerated . -0.238614 0 disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA nCoV-2019_75_RIGHT NA NA NA NA No co - mutations reported NA 0.00005791595999 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.0000599484443378694),Asia(0.0000910145083868184),Europe(0.0000457296036862107),NorthAmerica(0.0000567364212909967),Oceania(0.0000238834487700024),SouthAmerica(0.000305891039502136) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85897&&LOCATION=1:22896:T:C
23009G>A 1 23009 G A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V483I None - None 0.68 Tolerated -1.71 1.50929 0.023622 Disulf_bond BetaCoV_S1-CTD NA NA Surface glycoprotein_STEIYQAGSTPCNGV NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.00005243149408 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an decreased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000199828147792898),Asia(0.0000202254463081819),Europe(0.000063535821050753),NorthAmerica(0.0000367851522655913),SouthAmerica(0.000168767470070144) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef859e8&&LOCATION=1:23009:G:A
23090G>C 1 23090 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V510L None - None 0.51 Tolerated 1.65 4.256 0.409449 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_QPYRVVVLSFELLHA 14 Surface glycoprotein_QPYRVVVL -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00001053017454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.00000674181543606062),Europe(0.0000133546630234067),NorthAmerica(0.00000810520304157096) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85ae8&&LOCATION=1:23090:G:C
23090G>T 1 23090 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V510L None - None 0.51 Tolerated 1.65 4.256 0.409449 Disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_QPYRVVVLSFELLHA 14 Surface glycoprotein_QPYRVVVL -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.00001053017454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Infectivity of 106 pseudotyped viruses possessing 80 natural variants and 26 glycosylation mutants were tested using 293T-hACE2 cells, where a difference by 4-fold in RLU compared with the reference Wuhan-1 strain (GenBank: MN_908947) was deemed as being significant. This combination of co-occurring mutations were found to have significantly decreased infectivity in comparison to the reference strain Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Africa(0.0000199828147792898),Asia(0.0000842726929507578),Europe(0.000128285702376361),NorthAmerica(0.0000773111674734461),Oceania(0.0000238834487700024),SouthAmerica(0.000073835768155688) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85ae9&&LOCATION=1:23090:G:T
23405G>C 1 23405 G C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 V615L None - None 0.66 Tolerated 1.65 4.256 1 NA NA NA NA Surface glycoprotein_FGGVSVITPGTNTSNQVAVLYQDVNCTEV NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.00003466182454 Experimental pcDNA3.1.S2 recombinant plasmid (GenBank: MT_613044), constructed by inserted the codon-optimized S gene of SARS-CoV-2 (GenBank: MN_908947) into pcDNA3.1, was used as the template to generate the plasmid with mutagenesises in S gene.This was followed by production and titration of pseudotyped viruses and their quantification by RT-PCR Sensitivity of the strains with amino acid changes to ten COVID-19 convalescent sera was determined. Modest differences between variants and reference strain (within 4-fold) were observed in their reactivity to grouped convalescent sera.These co-occurring mutations were found to have an increased infectivity compared to the reference strain via cell line studies Li, Q., Wu, J., Nie, J., Zhang, L., Hao, H., Liu, S., Zhao, C., Zhang, Q., Liu, H., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Zhang, L., Li, X., Huang, W., & Wang, Y. (2020). The Impact of Natural and Glycosylation Mutations in the SARS-CoV-2 Spike Protein on Viral Infectivity and Antigenicity. SSRN Electronic Journal, 1. https://doi.org/10.2139/ssrn.3635800 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7366990/ The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity Qianqian Li, Jiajing Wu, Jianhui Nie, Li Zhang, Huan Hao, Shuo Liu, Chenyan Zhao, Qi Zhang, Huan Liu, Lingling Nie, Haiyang Qin, Meng Wang, Qiong Lu, Xiaoyu Li, Qiyu Sun, Junkai Liu, Linqi Zhang, Xuguang Li, Weijin Huan and Youchun Wang Asia(0.0000101127231540909),Europe(0.0000566561461599071),NorthAmerica(0.0000093521573556588) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85e86&&LOCATION=1:23405:G:C
22920A>T 1 22920 A T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y453F None - None 0.62 Tolerated 1.65 2.25839 0.173228 disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_YLYRLFRKSNLKPFE 9.2 Surface glycoprotein_NYNYLYRLF -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.0002867278777 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.000239793777351478),Asia(0.0000235963540262122),Europe(0.000484005362908921),NorthAmerica(0.0000573598984480407) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef858e0&&LOCATION=1:22920:A:T
23084T>C 1 23084 T C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Y508H None - None 0.56 Tolerated -3.3 -1.61197 0 disulf_bond BetaCoV_S1-CTD NA NA NA Surface glycoprotein_QPYRVVVLSFELLHA 14 Surface glycoprotein_QPYRVVVL -1 NA NA NA NA NA NA NA No co - mutations reported NA 0.000214771685 Experimental Large collection of highly-potent fully human neutralizing antibodies targeting the RBD of the spike protein of SARS-CoV-2 was generated utilizing genetically-humanized mice and B cells from convalescent humans. Efficacy of antiviral antibodies against the breadth of spike RBD variants represented in publicly available SARS-CoV-2 sequences was identified using the VSV pseudoparticle system expressing the SARS-CoV-2 spike variants. Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. The variant was encoded into pVSV-SARS-CoV-2-S (mNeon) pseudoparticles and neutralization assays were performed in Vero cells. There was no observed neutralization with hIgG1 isotype control (N/A). Baum, A., Fulton, B. O., Wloga, E., Copin, R., Pascal, K. E., Russo, V., Giordano, S., Lanza, K., Negron, N., Ni, M., Wei, Y., Atwal, G. S., Murphy, A. J., Stahl, N., Yancopoulos, G. D., & Kyratsous, C. A. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, eabd0831. https://doi.org/10.1126/science.abd0831 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299283/ Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Alina Baum, Benjamin O. Fulton, Elzbieta Wloga, Richard Copin, Kristen E. Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Andrew J. Murphy, Neil Stahl, George D. Yancopoulos, and Christos A. Kyratsous Africa(0.000919209479847331),Asia(0.000117981770131061),Europe(0.000268712007501274),NorthAmerica(0.00012407195425174),Oceania(0.0000716503463100072),SouthAmerica(0.000337534940140288) https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0 http://clingen.igib.res.in/indicov/showdata.php?id=5f8d54af6dcd0a2abef85ad4&&LOCATION=1:23084:T:C
21991TTATTAC>T 1 21991 TTATTAC T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ144-145YY 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4 McCarthy, K. R., Rennick, L. J., Nambulli, S., Robinson-McCarthy, L. R., Bain, W. G., Haidar, G., & Duprex, W. P. (2021). Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science (New York, N.Y.), 371(6534), 1139–1142. https://doi.org/10.1126/science.abf6950 https://pubmed.ncbi.nlm.nih.gov/33536258/ Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. 0
21991TTATTAC>T 1 21991 TTATTAC T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ144-145YY 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4 Ribes, M., Chaccour, C., & Moncunill, G. (2021). Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain. Signal transduction and targeted therapy, 6(1), 164.https://doi.org/10.1038/s41392-021-00601-8 https://pubmed.ncbi.nlm.nih.gov/33895775/ Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain Marta Ribes, Carlos Chaccour, Gemma Moncunill##Kevin R McCarthy, Linda J Rennick, Sham Nambulli, Lindsey R Robinson-McCarthy, William G Bain, Ghady Haidar, W Paul Duprex##Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R Fontes-Garfias, Hongjie Xia, Kena A Swanson, Mark Cutler, David Cooper, Vineet D Menachery, Scott C Weaver, Philip R Dormitzer, Pei-Yong Shi 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
21991TTATTAC>T 1 21991 TTATTAC T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ144-145YY 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4 Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature medicine, 27(4), 620–621. https://doi.org/10.1038/s41591-021-01270-4 https://pubmed.ncbi.nlm.nih.gov/33558724/ Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. 0
22030G>T 1 22030 G T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ157-158 B.1.617.2 https://outbreak.info/situation-reports?pango=B.1.617.2 Characteristic mutation of B.1.617.2 lineage 0 Experimental Neutralization assays for vaccine sera The neutralization efficacy of the VUI B.1.617 variant was compared with prototype strain B1 (D614G) and B.1.1.7 variant using sera of 28 BBV152 (Covaxin) vaccinated individuals, collected during the phase II clinical trial. For D614G vs. B.1.617, the GMT ratio was 1.95, (95% CI:1.60 - 2.38 and p-value <0.0001) resulting in a statistically difference. Similarly, the GMT ratio comparison of B.1.1.7 was significantly higher than the GMT for B.1.617 (GMT ratio 1.84, 95% CI: 1.50 - 2.27, p value< 0.0001) and the CI was not within the equivalence interval (Figure 1 C and 1D). The comparison of D614G and B.1.1.7 showed equivalent responses with a GMT ratio of 1.06 which is close to 1, and the 95% CI (1.02 to 1.10) was well within the statistical equivalence. Yadav, P. D., Sapkal, G. N., Abraham, P., Ella, R., Deshpande, G., Patil, D. Y., Nyayanit, D. A., Gupta, N., Sahay, R. R., Shete, A. M., Panda, S., Bhargava, B., & Mohan, V. K. (2021). Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciab411. Advance online publication. https://doi.org/10.1093/cid/ciab411 https://pubmed.ncbi.nlm.nih.gov/33961693/ Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees Pragya D Yadav 1, Gajanan N Sapkal 1, Priya Abraham 1, Raches Ella 2, Gururaj Deshpande 1, Deepak Y Patil 1, Dimpal A Nyayanit 1, Nivedita Gupta 3, Rima R Sahay 1, Anita M Shete 1, Samiran Panda 3, Balram Bhargava 3, V Krishna Mohan 2 0
21619A>C 1 21619 A C S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ19-S 0 Experimental Generation of stable cell lines with hACE-2-mCheny, SARS-CoV-2 Spike-full and -C terminal Δ19-EGFP Widely used to increase SARS-CoV-2 pseudovirus production for in vitro assays. Comparison of cell fusion occurring via Δ19-S expressing cells shows defective nuclear fusion and syncytia formation compared to WT-S. This distinction between the Δ19-S variant and WT-S protein may have downstream implications for studies that utilize pseudovirus-based entry assays. Chen, C. H., Badeti, S., Cho, J. H., Naghizadeh, A., Wang, X., & Liu, D. (2021). Deletion of ER-retention Motif on SARS-CoV-2 Spike Protein Reduces Cell Hybrid During Cell-cell Fusion. Research square, rs.3.rs-380389. https://doi.org/10.21203/rs.3.rs-380389/v1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043463/ Deletion of ER-retention Motif on SARS-CoV-2 Spike Protein Reduces Cell Hybrid During Cell-cell Fusion Chih-Hsiung Chen, Saiaditya Badeti, Jong Hyun Cho, Alireza Naghizadeh, Xuening Wang, and Dongfang Liu 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22222T>A 1 22222 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ220 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays McCarthy, K. R., Rennick, L. J., Nambulli, S., Robinson-McCarthy, L. R., Bain, W. G., Haidar, G., & Duprex, W. P. (2021). Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science (New York, N.Y.), 371(6534), 1139–1142. https://doi.org/10.1126/science.abf6950 https://pubmed.ncbi.nlm.nih.gov/33536258/ Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. 0
22222T>A 1 22222 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ220 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays Ribes, M., Chaccour, C., & Moncunill, G. (2021). Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain. Signal transduction and targeted therapy, 6(1), 164.https://doi.org/10.1038/s41392-021-00601-8 https://pubmed.ncbi.nlm.nih.gov/33895775/ Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain Marta Ribes, Carlos Chaccour, Gemma Moncunill##Kevin R McCarthy, Linda J Rennick, Sham Nambulli, Lindsey R Robinson-McCarthy, William G Bain, Ghady Haidar, W Paul Duprex##Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R Fontes-Garfias, Hongjie Xia, Kena A Swanson, Mark Cutler, David Cooper, Vineet D Menachery, Scott C Weaver, Philip R Dormitzer, Pei-Yong Shi 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22222T>A 1 22222 T A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ220 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature medicine, 27(4), 620–621. https://doi.org/10.1038/s41591-021-01270-4 https://pubmed.ncbi.nlm.nih.gov/33558724/ Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. 0
22288TGCTTTA>T 1 22288 TGCTTTA T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ243–244AL 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4 McCarthy, K. R., Rennick, L. J., Nambulli, S., Robinson-McCarthy, L. R., Bain, W. G., Haidar, G., & Duprex, W. P. (2021). Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science (New York, N.Y.), 371(6534), 1139–1142. https://doi.org/10.1126/science.abf6950 https://pubmed.ncbi.nlm.nih.gov/33536258/ Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. 0
22288TGCTTTA>T 1 22288 TGCTTTA T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ243–244AL 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4 Ribes, M., Chaccour, C., & Moncunill, G. (2021). Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain. Signal transduction and targeted therapy, 6(1), 164.https://doi.org/10.1038/s41392-021-00601-8 https://pubmed.ncbi.nlm.nih.gov/33895775/ Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain Marta Ribes, Carlos Chaccour, Gemma Moncunill##Kevin R McCarthy, Linda J Rennick, Sham Nambulli, Lindsey R Robinson-McCarthy, William G Bain, Ghady Haidar, W Paul Duprex##Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R Fontes-Garfias, Hongjie Xia, Kena A Swanson, Mark Cutler, David Cooper, Vineet D Menachery, Scott C Weaver, Philip R Dormitzer, Pei-Yong Shi 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
22288TGCTTTA>T 1 22288 TGCTTTA T S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ243–244AL 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4 Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature medicine, 27(4), 620–621. https://doi.org/10.1038/s41591-021-01270-4 https://pubmed.ncbi.nlm.nih.gov/33558724/ Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. 0
21766ACATG>A 1 21766 ACATG A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ69–70HV 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4.##Three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y + D614G from UK; and E484K + N501Y + D614G from SA were engineered. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses. McCarthy, K. R., Rennick, L. J., Nambulli, S., Robinson-McCarthy, L. R., Bain, W. G., Haidar, G., & Duprex, W. P. (2021). Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science (New York, N.Y.), 371(6534), 1139–1142. https://doi.org/10.1126/science.abf6950 https://pubmed.ncbi.nlm.nih.gov/33536258/ Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. 0
21766ACATG>A 1 21766 ACATG A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ69–70HV 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4.##Three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y + D614G from UK; and E484K + N501Y + D614G from SA were engineered. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses. Ribes, M., Chaccour, C., & Moncunill, G. (2021). Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain. Signal transduction and targeted therapy, 6(1), 164.https://doi.org/10.1038/s41392-021-00601-8 https://pubmed.ncbi.nlm.nih.gov/33895775/ Adapt or perish: SARS-CoV-2 antibody escape variants defined by deletions in the Spike N-terminal Domain Marta Ribes, Carlos Chaccour, Gemma Moncunill##Kevin R McCarthy, Linda J Rennick, Sham Nambulli, Lindsey R Robinson-McCarthy, William G Bain, Ghady Haidar, W Paul Duprex##Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R Fontes-Garfias, Hongjie Xia, Kena A Swanson, Mark Cutler, David Cooper, Vineet D Menachery, Scott C Weaver, Philip R Dormitzer, Pei-Yong Shi 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
21766ACATG>A 1 21766 ACATG A S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 Δ69–70HV 0 Experimental S genes were cloned directly from clinical material obtained 72 days after COVID-19 diagnosis. This was followed by sequence analysis and immunofluroscence assays With indirect immunofluorescence, the 48A- neutralizing monoclonal antibody did not bind to the S protein when carrying the deletions: Δ69–70 + Δ144/145 (RDR1 + 2), Δ141–145 or Δ144/145 or Δ146 in RDR2, and Δ243–244 in RDR4.##Three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y + D614G from UK; and E484K + N501Y + D614G from SA were engineered. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses. Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature medicine, 27(4), 620–621. https://doi.org/10.1038/s41591-021-01270-4 https://pubmed.ncbi.nlm.nih.gov/33558724/ Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. 0
23593GACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTA GT>G 1 23593 GACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTA GT G S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Deletion Deletion Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 ΔPRRA 0 Experimental Both wild-type and mutant viruses were derived from the SARS-CoV-2 USA-WA1/2020 infectious clone. For ΔPRRA construction, the mutation was introduced into a subclone puc57-CoV2-F6 by using overlap PCR with primers ΔPRRA-F (5′-GACTAATTCTCGTAGTGTAGCTAGTCAATCCATC-3′) and ΔPRRA-R (5ʹ-GACTAGCTACACTACGAGAATTAGTCTGAGTC-3′). This was followed by deep sequencing analysis, Plaque-reduction neutralization test and infection studies Replicates of ΔPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, the neutralization values of sera from patients with coronavirus disease 2019 (COVID-19) and monoclonal antibodies against the receptor-binding domain of SARS-CoV-2 were lower against the ΔPRRA mutant than against parental SARS-CoV-2, probably owing to an increased ratio of particles to plaque-forming units in infections with the former. Johnson, B. A., Xie, X., Bailey, A. L., Kalveram, B., Lokugamage, K. G., Muruato, A., Zou, J., Zhang, X., Juelich, T., Smith, J. K., Zhang, L., Bopp, N., Schindewolf, C., Vu, M., Vanderheiden, A., Winkler, E. S., Swetnam, D., Plante, J. A., Aguilar, P., . . . Menachery, V. D. (2021). Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature, 591(7849), 293–299. https://doi.org/10.1038/s41586-021-03237-4 https://pubmed.ncbi.nlm.nih.gov/33494095/ Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis Bryan A Johnson # 1, Xuping Xie # 2, Adam L Bailey # 3, Birte Kalveram 4, Kumari G Lokugamage 1, Antonio Muruato 1, Jing Zou 2, Xianwen Zhang 2, Terry Juelich 4, Jennifer K Smith 4, Lihong Zhang 4, Nathen Bopp 4, Craig Schindewolf 1, Michelle Vu 1, Abigail Vanderheiden 5 6, Emma S Winkler 3 7, Daniele Swetnam 2, Jessica A Plante 1, Patricia Aguilar 4, Kenneth S Plante 1, Vsevolod Popov 4, Benhur Lee 8, Scott C Weaver 1 9, Mehul S Suthar 5 6 10, Andrew L Routh 2, Ping Ren 4, Zhiqiang Ku 11, Zhiqiang An 11, Kari Debbink 12, Michael S Diamond 3 7 13, Pei-Yong Shi 2 9, Alexander N Freiberg 4 9, Vineet D Menachery 14 15 0 https://genome.ucsc.edu/cgi-bin/hgTracks?hgtgroup_map_close=0&hgtgroup_genes_close=0&hgtgroup_uniprot_close=0&hgtgroup_immu_close=0&hgtgroup_rna_close=0&hgtgroup_regulation_close=0&hgtgroup_compGeno_close=0&hgtgroup_varRep_close=0&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E&position=NC_045512.2%3A21563-25384&hgt.positionInput=NC_045512.2%3A21563-25384&goButton=go&db=wuhCor1&c=NC_045512v2&l=265&r=21555&pix=950&dinkL=2.0&dinkR=2.0
S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 E484K B.1.1.7## B.1.351## P.1## B.1.525## P.3## B.1.620 https://outbreak.info/situation-reports?pango=B.1.1.7##https://outbreak.info/situation-reports?pango=B.1.351##https://outbreak.info/situation-reports?pango=P.1##https://outbreak.info/situation-reports?pango=B.1.525##https://outbreak.info/situation-reports?pango=P.3##https://outbreak.info/situation-reports?pango=B.1.620 Characteristic mutation of B.1.1.7, B.1.351, P.1, B.1.525, P.3 and B.1.620 lineages. 0.92 Tolerated -1.76 -2.61077 0 Disulf_bond BetaCoV_S1-CTD NA NA NA NA NA NA NA NA NA NA NA NA NA NA No co - mutations reported NA 0.0472352917 Experimental Binding of purified recombinant B.1.351 and B.1.1.7 RBD was compared with binding of the Hu-1 RBD, which was originally identified in Wuhan (SCoV2) using microscale thermophoresis. Increased affinity of binding to human ACE2 receptor. The B.1.351 RBD bound ACE2 with 4·62-times greater affinity than the SCoV2 RBD (mean Kd 87·6 nM [SD 25·5] vs 402·5 nM [112·1]; p=0·0009 Ramanathan, M., Ferguson, I. D., Miao, W., & Khavari, P. A. (2021). SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. The Lancet Infectious Diseases, 21(8), 1070. https://doi.org/10.1016/s1473-3099(21)00262-0 https://www.sciencedirect.com/science/article/pii/S1473309921002620?via%3Dihub SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. Africa(0.262654117458985),Asia(0.0539951998274095),Europe(0.0184638333467554),NorthAmerica(0.0578075550467982),Oceania(0.00449008836876045),SouthAmerica(0.502304730763145)
S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 K417N B.1.351 0.009496681788 Experimental Binding of purified recombinant B.1.351 and B.1.1.7 RBD was compared with binding of the Hu-1 RBD, which was originally identified in Wuhan (SCoV2) using microscale thermophoresis. Increased affinity of binding to human ACE2 receptor. The B.1.351 RBD bound ACE2 with 4·62-times greater affinity than the SCoV2 RBD (mean Kd 87·6 nM [SD 25·5] vs 402·5 nM [112·1]; p=0·0009 Ramanathan, M., Ferguson, I. D., Miao, W., & Khavari, P. A. (2021). SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. The Lancet Infectious Diseases, 21(8), 1070. https://doi.org/10.1016/s1473-3099(21)00262-0 https://www.sciencedirect.com/science/article/pii/S1473309921002620?via%3Dihub SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity Africa(0.230381871590432),Asia(0.0148825575751038),Europe(0.00714191191021458),NorthAmerica(0.00589497651985027),Oceania(0.00277048005732028),SouthAmerica(0.00132904382680238)
S 43740568 https://www.ncbi.nlm.nih.gov/gene/43740568 NC_045512.2:21563-25384 Single Nucleotide Variation Non Synonymous SNV Surface glycoprotein 1273 amino acids QHD43416.1 https://www.ncbi.nlm.nih.gov/protein/QHD43416.1 N501Y B.1.1.7##B.1.351 0.2844965776 Experimental Binding of purified recombinant B.1.351 and B.1.1.7 RBD was compared with binding of the Hu-1 RBD, which was originally identified in Wuhan (SCoV2) using microscale thermophoresis. Increased affinity of binding to human ACE2 receptor. The B.1.1.7 RBD bound ACE2 with 1·98-times greater affinity than the SCoV2 RBD (mean equilibrium dissociation constant [Kd] 203·7 nM [SD 57·1] vs 402·5 nM [112·1]; p=0·0521) Ramanathan, M., Ferguson, I. D., Miao, W., & Khavari, P. A. (2021). SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. The Lancet Infectious Diseases, 21(8), 1070. https://doi.org/10.1016/s1473-3099(21)00262-0 https://www.sciencedirect.com/science/article/pii/S1473309921002620?via%3Dihub SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity. Africa(0.278500489578962),Asia(0.242115446847527),Europe(0.338355765794823),NorthAmerica(0.204322193043491),Oceania(0.0219727728684022),SouthAmerica(0.488792785190655)
23062T>C 1 23062 T C ORF1ab 43740578 https://www.ncbi.nlm.nih.gov/gene/43740578 NC_045512.2:266-21555 Deletion Deletion ORF1ab Polyprotein 7096 amino acids QHD43415.1 https://www.ncbi.nlm.nih.gov/protein/QHD43415.1 Δ500-532 Δ500-532, an in-frame deletion of Nsp1 coding region, is negatively correlated with ESR, serum IFN-β level, and CD3+CD8+ T cell counts in the blood, also showed significant enrichment with non-severe (p adjust = 0.0071) but not severe traits . Association analysis Potential modulations in type I interferon response Lin, J. W., Tang, C., Wei, H. C., Du, B., Chen, C., Wang, M., Zhou, Y., Yu, M. X., Cheng, L., Kuivanen, S., Ogando, N. S., Levanov, L., Zhao, Y., Li, C. L., Zhou, R., Li, Z., Zhang, Y., Sun, K., Wang, C., Chen, L., … Chen, L. (2021). Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response. Cell host & microbe, 29(3), 489–502.e8. https://doi.org/10.1016/j.chom.2021.01.015 https://pubmed.ncbi.nlm.nih.gov/33548198/ Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response Jing-Wen Lin , Chao Tang , Han-Cheng Wei , Baowen Du , Chuan Chen , Minjin Wang , Yongzhao Zhou , Ming-Xia Yu , Lu Cheng , Suvi Kuivanen , Natacha S Ogando , Lev Levanov , Yuancun Zhao , Chang-Ling Li , Ran Zhou , Zhidan Li , Yiming Zhang , Ke Sun , Chengdi Wang , Li Chen , Xia Xiao , Xiuran Zheng , Sha-Sha Chen , Zhen Zhou , Ruirui Yang , Dan Zhang , Mengying Xu , Junwei Song , Danrui Wang , Yupeng Li , ShiKun Lei , Wanqin Zeng , Qingxin Yang , Ping He , Yaoyao Zhang , Lifang Zhou , Ling Cao , Feng Luo , Huayi Liu , Liping Wang , Fei Ye , Ming Zhang , Mengjiao Li , Wei Fan , Xinqiong Li , Kaiju Li , Bowen Ke , Jiannan Xu , Huiping Yang , Shusen He , Ming Pan , Yichen Yan , Yi Zha , Lingyu Jiang , Changxiu Yu , Yingfen Liu , Zhiyong Xu , Qingfeng Li , Yongmei Jiang , Jiufeng Sun , Wei Hong , Hongping Wei , Guangwen Lu , Olli Vapalahti , Yunzi Luo , Yuquan Wei , Thomas Connor , Wenjie Tan , Eric J Snijder , Teemu Smura , Weimin Li , Jia Geng , Binwu Ying , Lu Chen https://genome.ucsc.edu/cgi-bin/hgTracks?db=wuhCor1&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=NC_045512v2%3A266%2D21555&hgsid=950344573_A9vhn3kpWNAevyURQKIFZD7Av59E