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De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes

文献类型：期刊论文

作者Zhu, Yan9,11,12; Meng, Jiaolong10; Feng, Bo8; Zhao, Yao9; Zang, Yi1,8; Lu, Lingling10; Su, Mingbo8; Yang, Qi7; Zhang, Qi11,12; Feng, Lu
刊名STRUCTURE
出版日期2024-09-05
卷号32期号:9页码:12
ISSN号0969-2126
DOI10.1016/j.str.2024.05.019
通讯作者Zhao, Yao(zhaoyao@shanghaitech.edu.cn) ; Li, Jia(jli@simm.ac.cn) ; Jiang, Xuefeng(xfjiang@chem.ecnu.edu.cn) ; Rao, Zihe(raozh@mail.tsinghua.edu.cn)
英文摘要The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly all over the world. The main protease (Mpro) pro ) is significant to the replication and transcription of viruses, making it an attractive drug target against coronaviruses. Here, we introduce a series of novel inhibitors which are designed de novo through structure- based drug design approach that have great potential to inhibit SARS-CoV-2 M pro in vitro. . High-resolution structures show that these inhibitors form covalent bonds with the catalytic cysteine through the novel dibromomethyl ketone (DBMK) as a reactive warhead. At the same time, the designed phenyl group beside the DBMK warhead inserts into the cleft between H41 and C145 through p-p stacking interaction, splitting the catalytic dyad and disrupting proton transfer. This unique binding model provides novel clues for the cysteine protease inhibitor development of SARS-CoV-2 as well as other pathogens.
WOS关键词CLINICAL CHARACTERISTICS ; WUHAN
资助项目R&D Program of Guangzhou Laboratory[SRPG22-003] ; National Natural Science Foundation of China[32200131] ; National Natural Science Foundation of China[22125103] ; National Natural Science Foundation of China[21971065] ; Shenzhen High-level Hospital Construction Fund[23264G1001] ; Shenzhen Clinical Research Center for Tuberculosis[20210617141509001] ; Foundation of State Key Laboratory of Component-based Chinese Medicine[CBCM2020105] ; Science and Technology Commission of Shanghai Municipality[20XD1421500] ; Shanghai Municipal Science and Technology Major Project
WOS研究方向Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种英语
WOS记录号WOS:001308962700001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/313344]  
专题中国科学院上海药物研究所
通讯作者Zhao, Yao; Li, Jia; Jiang, Xuefeng; Rao, Zihe
作者单位1.Lingang Lab, Shanghai 200031, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
3.Tsinghua Univ, Sch Med, Beijing 100091, Peoples R China
4.Tsinghua Univ, Sch Life Sci, Lab Struct Biol, Beijing 100091, Peoples R China
5.Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China
6.Nankai Univ, Coll Life Sci, Frontiers Sci Ctr Cell Response, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China
7.Guangzhou Natl Lab, Guangzhou 510005, Guangdong, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
9.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Shenzhen 518112, Peoples R China
10.East China Normal Univ, Sch Chem & Mol Engn, State Key Lab Mol & Proc Engn, Shanghai 200062, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Yan,Meng, Jiaolong,Feng, Bo,et al. De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes[J]. STRUCTURE,2024,32(9):12.
APA Zhu, Yan.,Meng, Jiaolong.,Feng, Bo.,Zhao, Yao.,Zang, Yi.,...&Rao, Zihe.(2024).De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes.STRUCTURE,32(9),12.
MLA Zhu, Yan,et al."De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes".STRUCTURE 32.9(2024):12.

入库方式： OAI收割

来源：上海药物研究所

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