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Basic Characteristics of Mutations
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Mutation Site
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P681H |
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Mutation Site Sentence
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We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. |
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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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Delta |
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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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COVID-19
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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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HAT |
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Location
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Sichuan(China) |
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Literature Information
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PMID
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39286971
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Title
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SARS-CoV-2 Delta and Omicron variants resist spike cleavage by human airway trypsin-like protease
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Author
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Ren W,Hong W,Yang J,Zou J,Chen L,Zhou Y,Lei H,Alu A,Que H,Gong Y,Bi Z,He C,Fu M,Peng D,Yang Y,Yu W,Tang C,Huang Q,Yang M,Li B,Li J,Wang J,Ma X,Hu H,Cheng W,Dong H,Lei J,Chen L,Zhou X,Li J,Wang W,Lu G,Shen G,Yang L,Yang J,Wang Z,Jia G,Su Z,Shao B,Miao H,Yiu-Nam Lau J,Wei Y,Zhang K,Dai L,Lu S,Wei X
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Journal
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The Journal of clinical investigation
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Journal Info
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2024 Sep 17;134(18):e174304
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Abstract
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Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin-like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.
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Sequence Data
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-
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