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Basic Characteristics of Mutations
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Mutation Site
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N501Y |
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Mutation Site Sentence
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The identification of the N501Y substitution, which enhances ACE2 binding, before its emergence in the Alpha variant and fixation in Omicron variants highlights the power of deep-mutational scanning for prospective mapping of the effect of mutations to the SARS-CoV-2 RBD and motivates the characterization of unusual mutants, such as E406W. |
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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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Alpha(B.1.1.7);Omicron(BA.1;B.1.1.529) |
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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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ACE2
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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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