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Basic Characteristics of Mutations
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Mutation Site
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Q1005R |
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Mutation Site Sentence
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To experimentally validate our findings, S protein bearing S2 mutations D950N, Q954H, T961F, V987C, Q1005R, and Q1010W were individually expressed by transient transfection of HEK293T cells, which were subsequently analyzed by flow cytometry using COVA1-07, COVA2-14, COVA2-18, and CC12.3 (SI Appendix, Fig. S3). |
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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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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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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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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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38557175
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Title
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Evidence of antigenic drift in the fusion machinery core of SARS-CoV-2 spike
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Author
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Tan TJC,Verma AK,Odle A,Lei R,Meyerholz DK,Matreyek KA,Perlman S,Wong LR,Wu NC
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Journal
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Proceedings of the National Academy of Sciences of the United States of America
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Journal Info
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2024 Apr 9;121(15):e2317222121
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Abstract
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Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding domain of spike protein. In contrast, whether antigenic drift occurs in the S2 domain remains largely elusive. Here, we perform a deep mutational scanning experiment to identify S2 mutations that affect binding of SARS-CoV-2 spike to three S2 apex public antibodies. Our results indicate that spatially diverse mutations, including D950N and Q954H, which are observed in Delta and Omicron variants, respectively, weaken the binding of spike to these antibodies. Although S2 apex antibodies are known to be nonneutralizing, we show that they confer protection in vivo through Fc-mediated effector functions. Overall, this study indicates that the S2 domain of SARS-CoV-2 spike can undergo antigenic drift, which represents a potential challenge for the development of more universal coronavirus vaccines.
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Sequence Data
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PRJNA888135
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