Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease

American Association for the Advancement of Science (AAAS) - Tập 368 Số 6497 - Trang 1331-1335 - 2020
Wenhao Dai1,2, Bing Zhang3, Xia Jiang4, Haixia Su2,5, Jian Li6,2, Yao Zhao3, Xiong Xie2,5, Zhixing Jin3, Jingjing Peng2,5, Fengjiang Liu3, Chunpu Li2,5, You Li7, Fang Bai3, Haofeng Wang3, Xi Cheng2, Xiaobo Cen7, Shulei Hu2, Xiuna Yang3, Jiang Wang2,5, Xiang Liu8, Gengfu Xiao4, Hualiang Jiang1,3,2,5, Zihe Rao3, Leike Zhang4, Yechun Xu2,5, Haitao Yang3, Hong Liu6,1,2,5
1School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China
2State Key Laboratory of Drug Research, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
3Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
4State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China
5University of Chinese Academy of Sciences, Beijing, 100049, China
6College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Nanjing 210023, China.
7National Chengdu Center for Safety Evaluation of Drugs, Westchina Hospital of Sichuan University, High-Tech Development Zone, Chengdu, Sichuan 610041, China.
8State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Response, College of Life Sciences, College of Pharmacy, Nankai University, Tianjin 300353, China.

Tóm tắt

Promising antiviral protease inhibitors With no vaccine or proven effective drug against the virus that causes coronavirus disease 2019 (COVID-19), scientists are racing to find clinical antiviral treatments. A promising drug target is the viral main protease M pro , which plays a key role in viral replication and transcription. Dai et al. designed two inhibitors, 11a and 11b, based on analyzing the structure of the M pro active site. Both strongly inhibited the activity of M pro and showed good antiviral activity in cell culture. Compound 11a had better pharmacokinetic properties and low toxicity when tested in mice and dogs, suggesting that this compound is a promising drug candidate. Science , this issue p. 1331

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American Association for the Advancement of Science (AAAS)

Tập 368 Số 6497

1331-1335

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