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

文献类型：期刊论文

作者Dai, Wenhao2,3; Zhang, Bing4,5; Jiang, Xia-Ming1; Su, Haixia2,6; Li, Jian2,6; Zhao, Yao4,5; Xie, Xiong2,6; Jin, Zhenming4,5; Peng, Jingjing2,6; Liu, Fengjiang4,5
刊名SCIENCE
出版日期2020-06-19
卷号368期号:6497页码:1331-+
ISSN号0036-8075
DOI10.1126/science.abb4489
通讯作者Zhang, Lei-Ke(zhangleike@wh.iov.cn) ; Xu, Yechun(ycxu@simm.ac.cn) ; Yang, Haitao(yanght@shanghaitech.edu.cn) ; Liu, Hong(hliu@simm.ac.cn)
英文摘要SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, M-pro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting M-pro. Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 M-pro in complex with 11a or 11b, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of 11a and 11b are covalently bound to cysteine 145 of M-pro. Both compounds showed good pharmacokinetic properties in vivo, and 11a also exhibited low toxicity, which suggests that these compounds are promising drug candidates.
WOS关键词CORONAVIRUS ; INHIBITORS ; 3C
资助项目National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[21672231] ; National Natural Science Foundation of China[21877118] ; National Natural Science Foundation of China[31970165] ; National Natural Science Foundation of China[91953000] ; National Natural Science Foundation of China[81620108027] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040107] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12040201] ; Chinese Academy of Engineering[2020-CMKYGG-05] ; Science and Technology Commission of Shanghai Municipality[20431900100] ; Science and Technology Commission of Shanghai Municipality[20431900200] ; National Key R&D Program of China[2017YFC0840300] ; National Key R&D Program of China[2020YFC0841400] ; National Key R&D Program of China[2020YFA0707500] ; National Key R&D Program of China[2017YFB0202604] ; Department of Science and Technology of Guangxi Zhuang Autonomous Region[2020AB40007] ; Frontier Biotechnologies Inc. ; Ma Yun Foundation[2020-CMKYGG-05]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000544017600040
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/291902]  
专题新药研究国家重点实验室
通讯作者Zhang, Lei-Ke; Xu, Yechun; Yang, Haitao; Liu, Hong
作者单位1.Chinese Acad Sci, Ctr Biosafety Mega Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China
4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China
8.Sichuan Univ, Westchina Hosp, Natl Chengdu Ctr Safety Evaluat Drugs, Chengdu 610041, Sichuan, Peoples R China
9.Nankai Univ, State Key Lab Med Chem Biol, Frontiers Sci Ctr Cell Response, Coll Pharm,Coll Life Sci, Tianjin 300353, Peoples R China
推荐引用方式
GB/T 7714		 Dai, Wenhao,Zhang, Bing,Jiang, Xia-Ming,et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease[J]. SCIENCE,2020,368(6497):1331-+.
APA Dai, Wenhao.,Zhang, Bing.,Jiang, Xia-Ming.,Su, Haixia.,Li, Jian.,...&Liu, Hong.(2020).Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.SCIENCE,368(6497),1331-+.
MLA Dai, Wenhao,et al."Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease".SCIENCE 368.6497(2020):1331-+.

入库方式： OAI收割

来源：上海药物研究所

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