tetano
Editor, Senior Moderator
Nat Commun
. 2021 Apr 9;12(1):2114.
doi: 10.1038/s41467-021-22297-8.
GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein
Ming Zhao[SUP] #[/SUP][SUP] 1 2 [/SUP], Yu Yu[SUP] #[/SUP][SUP] 1 3 [/SUP], Li-Ming Sun[SUP] #[/SUP][SUP] 1 [/SUP], Jia-Qing Xing[SUP] 1 [/SUP], Tingting Li[SUP] 1 [/SUP], Yunkai Zhu[SUP] 4 [/SUP], Miao Wang[SUP] 1 [/SUP], Yin Yu[SUP] 4 [/SUP], Wen Xue[SUP] 1 [/SUP], Tian Xia[SUP] 1 [/SUP], Hong Cai[SUP] 1 [/SUP], Qiu-Ying Han[SUP] 1 [/SUP], Xiaoyao Yin[SUP] 1 [/SUP], Wei-Hua Li[SUP] 1 [/SUP], Ai-Ling Li[SUP] 1 [/SUP], Jiuwei Cui[SUP] 3 [/SUP], Zhenghong Yuan[SUP] 4 [/SUP], Rong Zhang[SUP] 4 [/SUP], Tao Zhou[SUP] 5 [/SUP], Xue-Min Zhang[SUP] 6 7 [/SUP], Tao Li[SUP] 8 9 [/SUP]
Affiliations
Abstract
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[SUP]R203K/G204R[/SUP] 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.
. 2021 Apr 9;12(1):2114.
doi: 10.1038/s41467-021-22297-8.
GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein
Ming Zhao[SUP] #[/SUP][SUP] 1 2 [/SUP], Yu Yu[SUP] #[/SUP][SUP] 1 3 [/SUP], Li-Ming Sun[SUP] #[/SUP][SUP] 1 [/SUP], Jia-Qing Xing[SUP] 1 [/SUP], Tingting Li[SUP] 1 [/SUP], Yunkai Zhu[SUP] 4 [/SUP], Miao Wang[SUP] 1 [/SUP], Yin Yu[SUP] 4 [/SUP], Wen Xue[SUP] 1 [/SUP], Tian Xia[SUP] 1 [/SUP], Hong Cai[SUP] 1 [/SUP], Qiu-Ying Han[SUP] 1 [/SUP], Xiaoyao Yin[SUP] 1 [/SUP], Wei-Hua Li[SUP] 1 [/SUP], Ai-Ling Li[SUP] 1 [/SUP], Jiuwei Cui[SUP] 3 [/SUP], Zhenghong Yuan[SUP] 4 [/SUP], Rong Zhang[SUP] 4 [/SUP], Tao Zhou[SUP] 5 [/SUP], Xue-Min Zhang[SUP] 6 7 [/SUP], Tao Li[SUP] 8 9 [/SUP]
Affiliations
- PMID: 33837182
- DOI: 10.1038/s41467-021-22297-8
Abstract
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[SUP]R203K/G204R[/SUP] 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.