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Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease

文献类型：期刊论文

作者Shen, Wen4,5; Chen, Xinyao2,3; Zhou, Liping1,4; Cheng, Yan1,4; Zhang, Yan1,4; Jiang, Xiangrui1,4; Sun, Haiguo1,4; Shen, Jingshan1,4,5
刊名BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
出版日期2024-11-01
卷号112页码:5
关键词COVID-19 SARS-CoV-2 3CL pro inhibitor Drug design Antiviral activities
ISSN号0960-894X
DOI10.1016/j.bmcl.2024.129942
通讯作者Sun, Haiguo(sunhaiguo@simm.ac.cn)
英文摘要COVID-19 has caused severe consequences in terms of public health and economy worldwide since its outbreak in December 2019. SARS-CoV-2 3C-like protease (3CL(pro)), crucial for the viral replications, is an attractive target for the development of antiviral drugs. In this study, several kinds of Michael acceptor warheads were utilized to hunt for potent covalent inhibitors against 3CLpro. Meanwhile, novel 3CL(pro )inhibitors with the P3-3,5-dichloro4-(2-(dimethylamino)ethoxy)phenyl moiety were designed and synthesized which may form salt bridge with residue Glu166. Among them, two compounds 12b and 12c exhibited high inhibitory activities against SARSCoV-2 3CL(pro). Further investigations suggested that 12b with an acrylate warhead displayed potent activity against HCoV-OC43 (EC50 = 97 nM) and SARS-CoV-2 replicon (EC50 = 45 nM) and low cytotoxicity (CC50 > 10 mu M) in Huh7 cells. Taken together, this study devised two series of 3CL(pro) inhibitors and provided the potent SARS-CoV-2 3CL(pro) inhibitor (12b) which may be used for treating coronavirus infections.
资助项目Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0120234003]
WOS研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:001309884300001
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/313290]  
专题新药研究国家重点实验室
通讯作者Sun, Haiguo
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Yangtze Delta Pharmaceut Coll, Yangtze Delta Drug Adv Res Inst, Nantong 226133, Peoples R China
3.Shenyang Pharmaceut Univ, Wuya Coll Innovat, Shenyang 110016, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Shen, Wen,Chen, Xinyao,Zhou, Liping,et al. Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2024,112:5.
APA Shen, Wen.,Chen, Xinyao.,Zhou, Liping.,Cheng, Yan.,Zhang, Yan.,...&Shen, Jingshan.(2024).Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,112,5.
MLA Shen, Wen,et al."Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 112(2024):5.

入库方式： OAI收割

来源：上海药物研究所

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