中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2

文献类型：期刊论文

作者Dai, Wenhao8,9; Jochmans, Dirk7; Xie, Hang9; Yang, Hang6; Li, Jian5,9; Su, Haixia8,9; Chang, Di4; Wang, Jiang3,8,9; Peng, Jingjing8,9; Zhu, Lili4
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2022-02-24
卷号65期号:4页码:2794-2808
ISSN号0022-2623
DOI10.1021/acs.jmedchem.0c02258
通讯作者Zhang, Leike(zhangleike@wh.iov.cn) ; Xu, Yechun(ycxu@simm.ac.cn) ; Neyts, Johan(johan.neyts@kuleuven.be) ; Liu, Hong(hliu@simm.ac.cn)
英文摘要A novel series of peptidomimetic aldehydes was designed and synthesized to target 3C protease (3C(pro)) of enterovirus 71 (EV71). Most of the compounds exhibited high antiviral activity, and among them, compound 18p demonstrated potent enzyme inhibitory activity and broad-spectrum antiviral activity on a panel of enteroviruses and rhinoviruses. The crystal structure of EV71 3C(pro) in complex with 18p determined at a resolution of 1.2 angstrom revealed that 18p covalently linked to the catalytic Cys147 with an aldehyde group. In addition, these compounds also exhibited good inhibitory activity against the 3CL(pro) and the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially compound 18p (IC50 = 0.034 mu M, EC50 = 0.29 mu M). According to our previous work, these compounds have no reasons for concern regarding acute toxicity. Compared with AG7088, compound 18p also exhibited good pharmacokinetic properties and more potent anticoronavirus activity, making it an excellent lead for further development.
WOS关键词ANTIVIRAL ACTIVITY ; 3C-LIKE PROTEASES ; 3C-PROTEASE INHIBITORS ; DOUBLE-BLIND ; RNA-BINDING ; 3C ; RUPINTRIVIR ; INFECTION ; DISEASE ; POTENT
资助项目National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[21672231] ; National Natural Science Foundation of China[21877122] ; National Natural Science Foundation of China[21877118] ; 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] ; Youth Innovation Promotion Association CAS[2018367]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000797940600005
源URL[http://119.78.100.183/handle/2S10ELR8/301477]  
专题新药研究国家重点实验室
通讯作者Zhang, Leike; Xu, Yechun; Neyts, Johan; Liu, Hong
作者单位1.Univ Lubeck, German Ctr Infect Res DZIF, D-23562 Lubeck, Germany
2.Univ Lubeck, Inst Mol Med, D-23562 Lubeck, Germany
3.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Beijing 100049, Peoples R China
4.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China
5.Nanjing Univ Chinese Med, Coll Pharm, Nanjing 210023, Peoples R China
6.Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China
7.Katholieke Univ Leuven, Dept Microbiol & Immunol, Lab Virol & Chemotherapy, Rega Inst Med Res, B-3000 Leuven, Belgium
8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Dai, Wenhao,Jochmans, Dirk,Xie, Hang,et al. Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022,65(4):2794-2808.
APA Dai, Wenhao.,Jochmans, Dirk.,Xie, Hang.,Yang, Hang.,Li, Jian.,...&Liu, Hong.(2022).Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2.JOURNAL OF MEDICINAL CHEMISTRY,65(4),2794-2808.
MLA Dai, Wenhao,et al."Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2".JOURNAL OF MEDICINAL CHEMISTRY 65.4(2022):2794-2808.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。