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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
The development of Coronavirus 3C-Like protease (3CLpro) inhibitors from 2010 to 2020
Yuzhi Liu1, Chengyuan Liang1, Liang Xin1
1Faculty of Pharmacy, Shaanxi University of Science & Technology, Xi'an, 710021, PR China.
Abstract:
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, 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 3CLpro inhibitors, 3CLpro PROTAC degraders are hypothesised to be next-generation anti-coronavirus drugs.
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