GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein.
Nat Commun
; 12(1): 2114, 2021 04 09.
Article
in English
| MEDLINE | ID: covidwho-1174670
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Replication
/
Catechin
/
Nucleocapsid Proteins
/
Amino Acid Substitution
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2021
Document Type:
Article
Affiliation country:
S41467-021-22297-8
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