典型文献
Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates
文献摘要：
Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies.Our previous study shows that SARS-CoV-2 structural envelope(2-E)protein forms a type of cation channel,and heterogeneously expression of 2-E channels causes host cell death.In this study we developed a cell-based high throughput screening(HTS)assay and used it to discover inhibitors against 2-E channels.Among 4376 compounds tested,34 hits with cell protection activity were found.Followed by an anti-viral analysis,15 compounds which could inhibit SARS-CoV-2 replication were identified.In electrophysiological experiments,three representatives showing inhibitory effect on 2-E channels were chosen for further characterization.Among them,proanthocyanidins directly bound to 2-E channel with binding affinity(KD)of 22.14 μM in surface plasmon resonance assay.Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker.Consistently,mutations of Glu 8 and Asn 15,two residues lining the proposed binding pocket,abolished the inhibitory effects of proanthocyanidins.The natural product proanthocyanidins are widely used as cosmetic,suggesting a potential of proanthocyanidins as disinfectant for external use.This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.
文献关键词：
中图分类号：
作者姓名：
Yi Wang;Sui Fang;Yan Wu;Xi Cheng;Lei-ke Zhang;Xu-rui Shen;Shuang-qu Li;Jian-rong Xu;Wei-juan Shang;Zhao-bing Gao;Bing-qing Xia
作者机构：
CAS Key Laboratory of Receptor Research,Stake Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan 430071,China;Academy of Integrative Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Department of Pharmacology and Chemical Biology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Zhongshan Institute of Drug Discovery,Institution for Drug Discovery Innovation,Chinese Academy of Science,Zhongshan 528400,China
文献出处：
引用格式：
[1]Yi Wang;Sui Fang;Yan Wu;Xi Cheng;Lei-ke Zhang;Xu-rui Shen;Shuang-qu Li;Jian-rong Xu;Wei-juan Shang;Zhao-bing Gao;Bing-qing Xia-.Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates)[J].中国药理学报（英文版）,2022(04):781-787
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AB值：
0.638287
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