中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates

文献类型:期刊论文

作者Wang, Yi1,2; Fang, Sui1; Wu, Yan3; Cheng, Xi1,2; Zhang, Lei-ke3; Shen, Xu-rui1,2; Li, Shuang-qu1,2; Xu, Jian-rong4,5; Shang, Wei-juan3; Gao, Zhao-bing1,2,6
刊名ACTA PHARMACOLOGICA SINICA
出版日期2021-07-22
页码7
ISSN号1671-4083
关键词SARS-CoV-2 envelope protein (2-E) cation channel high-throughput screening (HTS) anti-virus
DOI10.1038/s41401-021-00732-2
通讯作者Shang, Wei-juan(shangweijuan@wh.iov.cn) ; Gao, Zhao-bing(zbgao@simm.ac.cn) ; Xia, Bing-qing(xiabingqing@simm.ac.cn)
英文摘要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 (K-D) of 22.14 mu M 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.
WOS关键词NATURAL COMPOUNDS ; HUMAN SKIN ; PROANTHOCYANIDINS ; EXPRESSION ; CORONAVIRUS ; PROTEIN ; DIAGNOSTICS ; THERAPY ; BINDING ; GENE
资助项目National Science Fund of Distinguished Young Scholars[81825021] ; Fund of Youth Innovation Promotion Association[2019285] ; National Natural Science Foundation of China[81773707] ; National Natural Science Foundation of China[31700732] ; Fund of Shanghai Science and Technology Innovation Action Plan[20ZR1474200] ; National Key Research and Development Program of China[2020YFC0842000] ; Strategic Leading Science and Technology Projects of Chinese Academy of Sciences[XDA12050308] ; Fund of National Science and Technology Major Project[2018ZX09711002-002-006] ; Hubei Science and Technology Project[2020FCA003]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000675780300001
源URL[http://119.78.100.183/handle/2S10ELR8/296752]  
专题中国科学院上海药物研究所
通讯作者Shang, Wei-juan; Gao, Zhao-bing; Xia, Bing-qing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Stake Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, State Key Lab Virol, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Wuhan 430071, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Acad Integrat Med, Shanghai 201203, Peoples R China
5.Shanghai Jiao Tong Univ Sch Med, Dept Pharmacol & Chem Biol, Shanghai 200025, Peoples R China
6.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery Innovat, Zhongshan 528400, Peoples R China
推荐引用方式
GB/T 7714
Wang, Yi,Fang, Sui,Wu, Yan,et al. Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates[J]. ACTA PHARMACOLOGICA SINICA,2021:7.
APA Wang, Yi.,Fang, Sui.,Wu, Yan.,Cheng, Xi.,Zhang, Lei-ke.,...&Xia, Bing-qing.(2021).Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates.ACTA PHARMACOLOGICA SINICA,7.
MLA Wang, Yi,et al."Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates".ACTA PHARMACOLOGICA SINICA (2021):7.

入库方式: OAI收割

来源:上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。