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. Coronavirus nucleocapsid (N) protein is important for viral genome packaging and virion assembly. Here the authors show that natural chemical (-)-gallocatechin gallate (GCG) disrupts the liquid–liquid phase separation of N and inhibits SARS-CoV-2 replication.
【저자키워드】 SARS-CoV-2, Protein aggregation, 【초록키워드】 COVID-19, Treatment, coronavirus disease, viruses, Coronavirus disease 2019, coronavirus, knowledge, SARS-COV-2 infection, Genome, polymorphism, nucleocapsid protein, RNA, Protein, Viral, nucleocapsid, IFN, genomes, polyphenol, green tea, GISAID, SARS-CoV-2 replication, binding, Amino acid, GISAID database, Potential treatment, viral genome, amino acid substitutions, Trigger, triggers, leads, gallate, virion assembly, coding sequence, genome variant, greater, predicted, identify, inhibit, undergo, interfere, reveal, exhibit, disrupt, GCG, the SARS-CoV-2, 【제목키워드】 inhibit, disrupting, GCG,