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Basic Characteristics of Mutations
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Mutation Site
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G204R |
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Mutation Site Sentence
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Interestingly,NR203K/G204R exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. |
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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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N |
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Standardized Encoding Gene
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N
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Genotype/Subtype
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- |
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Viral Reference
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AY278741.1
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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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33837182
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Title
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GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein
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Author
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Zhao M,Yu Y,Sun LM,Xing JQ,Li T,Zhu Y,Wang M,Yu Y,Xue W,Xia T,Cai H,Han QY,Yin X,Li WH,Li AL,Cui J,Yuan Z,Zhang R,Zhou T,Zhang XM,Li T
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Journal
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Nature communications
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Journal Info
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2021 Apr 9;12(1):2114
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Abstract
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Lack of detailed knowledge of SARS-CoV-2 infection has been hampering the development of treatments for coronavirus disease 2019 (COVID-19). Here, we report that RNA triggers the liquid-liquid phase separation (LLPS) of the SARS-CoV-2 nucleocapsid protein, N. By analyzing all 29 proteins of SARS-CoV-2, we find that only N is predicted as an LLPS protein. We further confirm the LLPS of N during SARS-CoV-2 infection. Among the 100,849 genome variants of SARS-CoV-2 in the GISAID database, we identify that ~37% (36,941) of the genomes contain a specific trio-nucleotide polymorphism (GGG-to-AAC) in the coding sequence of N, which leads to the amino acid substitutions, R203K/G204R. Interestingly, N(R203K/G204R) exhibits a higher propensity to undergo LLPS and a greater effect on IFN inhibition. By screening the chemicals known to interfere with N-RNA binding in other viruses, we find that (-)-gallocatechin gallate (GCG), a polyphenol from green tea, disrupts the LLPS of N and inhibits SARS-CoV-2 replication. Thus, our study reveals that targeting N-RNA condensation with GCG could be a potential treatment for COVID-19.
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Sequence Data
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-
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