Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases

Wang, Wenjing1,3,5; Li, Wenkang1,3; Wen, Zhiyuan2; Wang, Chong2; Liu, Weilong6; Zhang, Yufang1,3; Liu, Juncheng1,3; Ding, Tianze1,3; Shuai, Lei2; Zhong, Gongxun2; Bu, Zhigao2; Qu, Lingbo1; Ren, Maozhi1,3,4,5; Li, Fuguang1,3,5

2022-10-01

10.1002/advs.202203499

ADVANCED SCIENCE   Impact Factor & Quartile

2198-3844

Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which urgently calls for effective broad-spectrum antivirals. RNA-dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan-coronaviral therapeutic target. Herein, based on cryo-electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block SARS-CoV-2 RdRp, thus inhibiting SARS-CoV-2 replication in both cellular and mouse infection models. GOS also acts as a potent inhibitor against the SARS-CoV-2 variant of concern (VOC) and exerts same inhibitory effects toward mutated RdRps of VOCs as the RdRp of the original SARS-CoV-2. Moreover, that the RdRp inhibitor GOS has broad-spectrum anti-coronavirus activity against alphacoronaviruses (porcine epidemic diarrhea virus and swine acute diarrhea syndrome coronavirus), betacoronaviruses (SARS-CoV-2), gammacoronaviruses (avian infectious bronchitis virus), and deltacoronaviruses (porcine deltacoronavirus) is showed. The findings demonstrate that GOS may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and other coronavirus outbreaks.

coronavirus gossypol natural product RNA-dependent RNA polymerase SARS-CoV-2

SCI

English

Others

National Key R&D Program of China[2020YFA0908002] ; National Natural Science Foundation of China["31621005","U1804231","31972469"] ; Key Science and Technology Research of Henan Province[222102310043]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000870560000001

WILEY

Web of Science

1.Zhengzhou Univ, Sch Agr Sci, State Key Lab Cotton Biol, Zhengzhou Res Base, Zhengzhou 450001, Henan, Peoples R China
2.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150069, Heilongjiang, Peoples R China
3.Chinese Acad Agr Sci, Inst Cotton Res, Anyang 455000, Henan, Peoples R China
4.Chinese Acad Agr Sci, Inst Urban Agr, Chengdu 610213, Sichuan, Peoples R China
5.Hainan Yazhou Bay Seed Lab, Sanya 572025, Hainan, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis,Inst Hepatol,Sch Med, Shenzhen 518112, Guangdong, Peoples R China

Wang, Wenjing,Li, Wenkang,Wen, Zhiyuan,et al. Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases[J]. ADVANCED SCIENCE,2022.

Wang, Wenjing.,Li, Wenkang.,Wen, Zhiyuan.,Wang, Chong.,Liu, Weilong.,...&Li, Fuguang.(2022).Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases.ADVANCED SCIENCE.

Wang, Wenjing,et al."Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases".ADVANCED SCIENCE (2022).