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
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2021-07-22 |
| 页码 | 7 |
| 关键词 | SARS-CoV-2 envelope protein (2-E) cation channel high-throughput screening (HTS) anti-virus |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/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 |
| WOS记录号 | WOS:000675780300001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 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
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