GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein

Ming Zhao, Yu Yu, Li-Ming Sun, Jia-Qing Xing, Tingting Li, Yunkai Zhu, Miao Wang, Yin Yu, Wen Xue, Tian Xia, Hong Cai, Qiu-Ying Han, Xiaoyao Yin, Wei-Hua Li, Ai-Ling Li, Jiuwei Cui, Zhenghong Yuan, Rong Zhang, Tao Zhou (), Xue-Min Zhang () and Tao Li ()
Additional contact information
Ming Zhao: National Center of Biomedical Analysis
Yu Yu: National Center of Biomedical Analysis
Li-Ming Sun: National Center of Biomedical Analysis
Jia-Qing Xing: National Center of Biomedical Analysis
Tingting Li: National Center of Biomedical Analysis
Yunkai Zhu: Fudan University
Miao Wang: National Center of Biomedical Analysis
Yin Yu: Fudan University
Wen Xue: National Center of Biomedical Analysis
Tian Xia: National Center of Biomedical Analysis
Hong Cai: National Center of Biomedical Analysis
Qiu-Ying Han: National Center of Biomedical Analysis
Xiaoyao Yin: National Center of Biomedical Analysis
Wei-Hua Li: National Center of Biomedical Analysis
Ai-Ling Li: National Center of Biomedical Analysis
Jiuwei Cui: The First Hospital of Jilin University
Zhenghong Yuan: Fudan University
Rong Zhang: Fudan University
Tao Zhou: Nanhu Laboratory
Xue-Min Zhang: National Center of Biomedical Analysis
Tao Li: National Center of Biomedical Analysis

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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, NR203K/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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22297-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22297-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22297-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().