热门
Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients
文献类型：期刊论文
| 作者 | Su, Hai-xia2,3; Yao, Sheng3,4 ; Zhao, Wen-feng2,5,6; Li, Min-jun7; Liu, Jia3,4; Shang, Wei-juan8; Xie, Hang2; Ke, Chang-qiang4; Hu, Hang-chen2,3; Gao, Mei-na2,3
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2020-07-31 |
| 页码 | 11 |
| ISSN号 | 1671-4083 |
| 关键词 | SARS-CoV-2 3CL protease traditional Chinese medicines Shuanghuanglian oral liquid baicalin baicalein |
| DOI | 10.1038/s41401-020-0483-6 |
| 通讯作者 | Bai, Fang(baifang@shanghaitech.edu.cn) ; Wu, Yan(wuyan@wh.iov.cn) ; Ye, Yang(yye@simm.ac.cn) ; Xu, Ye-chun(ycxu@simm.ac.cn) |
| 英文摘要 | Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment. |
| WOS关键词 | SARS ; CORONAVIRUS ; INHIBITORS ; DESIGN ; OPTIMIZATION ; REDUCTION ; DISCOVERY ; BAICALEIN ; AGLYCONE ; MODEL |
| 资助项目 | National Key R&D Program of China[2020YFC0841400] ; National Key R&D Program of China[2017YFB0202604] ; National Key R&D Program of China[2016YFA0502301] ; National Natural Science Foundation of China[91953000] ; National Natural Science Foundation of China[21877122] ; International Partnership Program of Chinese Academy of Sciences[153631KYSB20170043] ; Chinese Academy of Engineering and Jack Ma Foundation[2020-CMKYGG-05] ; Science and Technology Commission of Shanghai Municipality[20431900200] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000554332300002 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292234]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Bai, Fang; Wu, Yan; Ye, Yang; Xu, Ye-chun |
| 作者单位 | 1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Peoples R China 6.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Peoples R China 7.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai Synchrotron Radiat Facil, Shanghai 201210, Peoples R China 8.Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China 9.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Div Cardiol, Wuhan 430030, Peoples R China 10.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan 430030, Peoples R China |
| 推荐引用方式 GB/T 7714 | Su, Hai-xia,Yao, Sheng,Zhao, Wen-feng,et al. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients[J]. ACTA PHARMACOLOGICA SINICA,2020:11. |
| APA | Su, Hai-xia.,Yao, Sheng.,Zhao, Wen-feng.,Li, Min-jun.,Liu, Jia.,...&Xu, Ye-chun.(2020).Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.ACTA PHARMACOLOGICA SINICA,11. |
| MLA | Su, Hai-xia,et al."Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients".ACTA PHARMACOLOGICA SINICA (2020):11. |
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。