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Basic Characteristics of Mutations
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Mutation Site
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L452R |
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Mutation Site Sentence
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Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. |
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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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Wuhan-Hu-1;B.1.1.7;B.1.351 |
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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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35114110
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Title
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Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display
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Author
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Tanaka S,Olson CA,Barnes CO,Higashide W,Gonzalez M,Taft J,Richardson A,Martin-Fernandez M,Bogunovic D,Gnanapragasam PNP,Bjorkman PJ,Spilman P,Niazi K,Rabizadeh S,Soon-Shiong P
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Journal
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Cell reports
|
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Journal Info
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2022 Feb 8;38(6):110348
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Abstract
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The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.
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Sequence Data
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-
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