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

doi:10.1126/science.abb4489

	Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease
	Dai, Wenhao 7,8; Zhang, Bing 1,9; Jiang, Xia-Ming 2; Su, Haixia 3,7; Li, Jian 3,7; Zhao, Yao 1,9; Xie, Xiong 3,7; Jin, Zhenming 1,9; Peng, Jingjing 3,7; Liu, Fengjiang 1,9
刊名	SCIENCE
	2020-06-19
卷号	368 期号:6497 页码:1331-+
ISSN号	0036-8075
DOI	10.1126/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.
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关键词	CORONAVIRUS ; INHIBITORS ; 3C
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号	WOS:000544017600040
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291902]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Lei-Ke; Xu, Yechun; Yang, Haitao; Liu, Hong
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Ctr Biosafety Mega Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China 5.Nankai Univ, State Key Lab Med Chem Biol, Frontiers Sci Ctr Cell Response, Coll Pharm,Coll Life Sci, Tianjin 300353, Peoples R China 6.Sichuan Univ, Westchina Hosp, Natl Chengdu Ctr Safety Evaluat Drugs, Chengdu 610041, Sichuan, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China 9.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, 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-+.