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Basic Characteristics of Mutations
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Mutation Site
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E166V |
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Mutation Site Sentence
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Finally, we utilize our screening as a basis to identify E166V as a resistance-conferring mutation against the clinically used 3CLpro inhibitor, nirmatrelvir. |
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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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|
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Standardized Encoding Gene
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|
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Genotype/Subtype
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- |
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Viral Reference
|
-
|
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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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Clinical and Epidemiological Correlations
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Clinical Information
|
- |
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Treatment
|
nirmatrelvir |
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Location
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- |
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Literature Information
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PMID
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36029764
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Title
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Functional map of SARS-CoV-2 3CL protease reveals tolerant and immutable sites
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Author
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Iketani S,Hong SJ,Sheng J,Bahari F,Culbertson B,Atanaki FF,Aditham AK,Kratz AF,Luck MI,Tian R,Goff SP,Montazeri H,Sabo Y,Ho DD,Chavez A
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Journal
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Cell host & microbe
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Journal Info
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2022 Oct 12;30(10):1354-1362
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Abstract
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The SARS-CoV-2 3CL protease (3CL(pro)) is an attractive therapeutic target, as it is essential to the virus and highly conserved among coronaviruses. However, our current understanding of its tolerance to mutations is limited. Here, we develop a yeast-based deep mutational scanning approach to systematically profile the activity of all possible single mutants of the 3CL(pro) and validate a subset of our results within authentic viruses. We reveal that the 3CL(pro) is highly malleable and is capable of tolerating mutations throughout the protein. Yet, we also identify specific residues that appear immutable, suggesting that these may be targets for future 3CL(pro) inhibitors. Finally, we utilize our screening as a basis to identify E166V as a resistance-conferring mutation against the clinically used 3CL(pro) inhibitor, nirmatrelvir. Collectively, the functional map presented herein may serve as a guide to better understand the biological properties of the 3CL(pro) and for drug development against coronaviruses.
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Sequence Data
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PRJNA813935
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