Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease | |
Dai, Wenhao7,8; Zhang, Bing1,9; Jiang, Xia-Ming2; Su, Haixia3,7; Li, Jian3,7; Zhao, Yao1,9; Xie, Xiong3,7; Jin, Zhenming1,9; Peng, Jingjing3,7; Liu, Fengjiang1,9 | |
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-+. |
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