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Basic Characteristics of Mutations
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Mutation Site
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S371F |
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Mutation Site Sentence
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These results are reminiscent of the BA.2 and BA.4/5 S371F mutation, which dampens S309 binding via remodeling of the RBD helix comprising residues 364-372, which are outside the epitope of this mAb, likely by altering the N343 glycan conformation. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RBD |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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BA.2;BA.4/BA.5 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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USA |
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Literature Information
|
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PMID
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37300832
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Title
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Structural changes in the SARS-CoV-2 spike E406W mutant escaping a clinical monoclonal antibody cocktail
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Author
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Addetia A,Park YJ,Starr T,Greaney AJ,Sprouse KR,Bowen JE,Tiles SW,Van Voorhis WC,Bloom JD,Corti D,Walls AC,Veesler D
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Journal
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Cell reports
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Journal Info
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2023 Jun 27;42(6):112621
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Abstract
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Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated by the REGEN-COV therapeutic monoclonal antibody (mAb) COVID-19 cocktail and the AZD1061 (COV2-2130) mAb. Here, we show that this mutation remodels the receptor-binding site allosterically, thereby altering the epitopes recognized by these three mAbs and vaccine-elicited neutralizing antibodies while remaining functional. Our results demonstrate the spectacular structural and functional plasticity of the SARS-CoV-2 RBD, which is continuously evolving in emerging SARS-CoV-2 variants, including currently circulating strains that are accumulating mutations in the antigenic sites remodeled by the E406W substitution.
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Sequence Data
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EMD-26058;PDB: 7TPK;EMD-26056;PDB: 7TPI
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