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The development of Coronavirus 3C-Like protease (3CL^pro) inhibitors from 2010 to 2020.

ABSTRACT: This review fully describes the coronavirus 3CL^pro peptidomimetic inhibitors and nonpeptidic small molecule inhibitors developed from 2010 to 2020. Specifically, the structural characteristics, binding modes and SARs of these 3CL^pro inhibitors are expounded in detail by division into two categories: peptidomimetic inhibitors mainly utilize electrophilic warhead groups to covalently bind the 3CL^pro Cys145 residue and thereby achieve irreversible inhibition effects, whereas nonpeptidic small molecule inhibitors mainly interact with residues in the S1', S1, S2 and S4 pockets via hydrogen bonds, hydrophobic bonds and van der Waals forces. Based on the emerging PROTAC technology and the existing 3CL^pro inhibitors, 3CL^pro PROTAC degraders are hypothesised to be next-generation anti-coronavirus drugs.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7409838 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The development of Coronavirus 3C-Like protease (3CLpro) inhibitors from 2010 to 2020.

Liu Yuzhi Y Liang Chengyuan C Xin Liang L Ren Xiaodong X Tian Lei L Ju Xingke X Li Han H Wang Yongbo Y Zhao Qianqian Q Liu Hong H Cao Wenqiang W Xie Xiaolin X Zhang Dezhu D Wang Yu Y Jian Yanlin Y

European journal of medicinal chemistry 20200806

This review fully describes the coronavirus 3CLpro peptidomimetic inhibitors and nonpeptidic small molecule inhibitors developed from 2010 to 2020. Specifically, the structural characteristics, binding modes and SARs of these 3CLpro inhibitors are expounded in detail by division into two categories: peptidomimetic inhibitors mainly utilize electrophilic warhead groups to covalently bind the 3CLpro Cys145 residue and thereby achieve irreversible inhibition effects ...[more]

PMID: 32810751

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