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Basic Characteristics of Mutations
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Mutation Site
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F486P |
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Mutation Site Sentence
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However, several currently circulating variants harbor amino acid mutations generated through multiple nucleotide substitutions (e.g., BA.1 S371L, BA.2.3.20 E484R, or XBB.1.5 G339H, V445P, and F486P) as well as mutations that dampen ACE2 binding in the Wuhan-Hu-1 background but are tolerated through epistatic interactions with other mutations (e.g., Q498R found in Omicron lineages). |
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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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XBB.1.5 |
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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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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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