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

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

  • Nat Commun. 2021 Apr 9;12(1):2114. doi: 10.1038/s41467-021-22297-8.
Ming Zhao  # 1 2,  Yu Yu  # 1 3,  Li-Ming Sun  # 1,  Jia-Qing Xing 1,  Tingting Li 1,  Yunkai Zhu 4,  Miao Wang 1,  Yin Yu 4,  Wen Xue 1,  Tian Xia 1,  Hong Cai 1,  Qiu-Ying Han 1,  Xiaoyao Yin 1,  Wei-Hua Li 1,  Ai-Ling Li 1,  Jiuwei Cui 3,  Zhenghong Yuan 4,  Rong Zhang 4,  Tao Zhou 5,  Xue-Min Zhang 6 7,  Tao Li 8 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Proteomics, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing, 100850, China.
  • 2 Nanhu Laboratory, Jiaxing, Zhejiang Province, 314002, China.
  • 3 Cancer Research Institute of Jilin University, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
  • 4 School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • 5 Nanhu Laboratory, Jiaxing, Zhejiang Province, 314002, China. tzhou@nanhulab.ac.cn.
  • 6 State Key Laboratory of Proteomics, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing, 100850, China. zhangxuemin@cashq.ac.cn.
  • 7 School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. zhangxuemin@cashq.ac.cn.
  • 8 State Key Laboratory of Proteomics, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing, 100850, China. tli@ncba.ac.cn.
  • 9 School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. tli@ncba.ac.cn.
  • # Contributed equally.
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, 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.

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