Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases

文献类型： 外文期刊

第一作者： Wang, Wenjing

作者： Wang, Wenjing;Li, Wenkang;Zhang, Yufang;Liu, Juncheng;Ding, Tianze;Qu, Lingbo;Ren, Maozhi;Li, Fuguang;Wen, Zhiyuan;Wang, Chong;Shuai, Lei;Zhong, Gongxun;Bu, Zhigao;Wang, Wenjing;Li, Wenkang;Zhang, Yufang;Liu, Juncheng;Ding, Tianze;Ren, Maozhi;Li, Fuguang;Ren, Maozhi;Wang, Wenjing;Ren, Maozhi;Li, Fuguang;Liu, Weilong

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关键词： coronavirus; gossypol; natural product; RNA-dependent RNA polymerase; SARS-CoV-2

期刊名称：ADVANCED SCIENCE （ 影响因子：17.521； 五年影响因子：18.939 ）

ISSN：

年卷期： 2022 年 9 卷 35 期

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收录情况： SCI

摘要： 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.

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