文献类型：期刊文献

英文题名：A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors

作者：Ren, Peng-xuan[1,2];Shang, Wei-juan[3];Yin, Wan-chao[4];Ge, Huan[5];Wang, Lin[1,2];Zhang, Xiang-lei[1,2];Li, Bing-qian[1,2,6];Li, Hong-lin[5];Xu, Ye-chun[4,7];Xu, Eric H.[4,7];Jiang, Hua-liang[1,2,4,7];Zhu, Li-li[5];Zhang, Lei-ke[3];Bai, Fang[1,2]

机构：[1]ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China;[2]ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China;[3]Chinese Acad Sci, Ctr Biosafety Mega Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Drug Design, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[6]Imperial Coll London, Dept Chem, London, England;[7]Univ Chinese Acad Sci, Beijing 100049, Peoples R China

年份：2022

卷号：43

期号：2

起止页码：483

外文期刊名：ACTA PHARMACOLOGICA SINICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000644822100001)】；

基金：This work was supported by the Science and Technology Commission of Shanghai Municipality grants (Grant IDs: 20431900102, 20431900100, and 20430780300); Shanghai Science and Technology Development Funds (Grant ID: 20QA1406400); the Youth Innovation Promotion Association CAS (grants 2018367 to L.-K.Z). the National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program", China (Grant ID: 2018ZX09711002); National Natural Science Foundation of China (No. 82003654); as well as the start-up package from ShanghaiTech University.

语种：英文

外文关键词：SARS-CoV-2 inhibitors; RdRp; host ribosome; Virus RNA

摘要：The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.