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Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases

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 synthes...

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Autores principales: Wang, Wenjing, Li, Wenkang, Wen, Zhiyuan, Wang, Chong, Liu, Weilong, Zhang, Yufang, Liu, Juncheng, Ding, Tianze, Shuai, Lei, Zhong, Gongxun, Bu, Zhigao, Qu, Lingbo, Ren, Maozhi, Li, Fuguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762316/
https://www.ncbi.nlm.nih.gov/pubmed/36266926
http://dx.doi.org/10.1002/advs.202203499
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author Wang, Wenjing
Li, Wenkang
Wen, Zhiyuan
Wang, Chong
Liu, Weilong
Zhang, Yufang
Liu, Juncheng
Ding, Tianze
Shuai, Lei
Zhong, Gongxun
Bu, Zhigao
Qu, Lingbo
Ren, Maozhi
Li, Fuguang
author_facet Wang, Wenjing
Li, Wenkang
Wen, Zhiyuan
Wang, Chong
Liu, Weilong
Zhang, Yufang
Liu, Juncheng
Ding, Tianze
Shuai, Lei
Zhong, Gongxun
Bu, Zhigao
Qu, Lingbo
Ren, Maozhi
Li, Fuguang
author_sort Wang, Wenjing
collection PubMed
description 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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spelling pubmed-97623162022-12-20 Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases Wang, Wenjing Li, Wenkang Wen, Zhiyuan Wang, Chong Liu, Weilong Zhang, Yufang Liu, Juncheng Ding, Tianze Shuai, Lei Zhong, Gongxun Bu, Zhigao Qu, Lingbo Ren, Maozhi Li, Fuguang Adv Sci (Weinh) Research Articles 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. John Wiley and Sons Inc. 2022-10-20 /pmc/articles/PMC9762316/ /pubmed/36266926 http://dx.doi.org/10.1002/advs.202203499 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Wang, Wenjing
Li, Wenkang
Wen, Zhiyuan
Wang, Chong
Liu, Weilong
Zhang, Yufang
Liu, Juncheng
Ding, Tianze
Shuai, Lei
Zhong, Gongxun
Bu, Zhigao
Qu, Lingbo
Ren, Maozhi
Li, Fuguang
Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
title Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
title_full Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
title_fullStr Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
title_full_unstemmed Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
title_short Gossypol Broadly Inhibits Coronaviruses by Targeting RNA‐Dependent RNA Polymerases
title_sort gossypol broadly inhibits coronaviruses by targeting rna‐dependent rna polymerases
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762316/
https://www.ncbi.nlm.nih.gov/pubmed/36266926
http://dx.doi.org/10.1002/advs.202203499
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