期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：8
页码：1
DOI：10.1073/pnas.2024420118
出版社：The National Academy of Sciences of the United States of America
摘要：Li et al. (1) recently report the discovery of 16 Food and Drug Administration–approved drugs as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. They were identified from a computational virtual screening approach using the Mpro as the drug target, and their enzymatic inhibition against SARS-CoV-2 Mpro was validated in the fluorescence resonance energy transfer (FRET)-based enzymatic assay (inhibitory constant Ki = 0.04 to 3.27 µM). Among the list of 16 discovered hits, disulfiram was recently proved by us as a nonspecific promiscuous cysteine protease inhibitor that not only inhibits SARS-CoV-2 Mpro but also five other cysteine proteases, and the inhibition was only observed in the absence of reducing reagent, 1,4-dithiothreitol (DTT) (2). As these claimed hits do not share structural similarities with existing Mpro inhibitors (3), we therefore chose the eight most potent compounds, including dipyridamole, candesartan cilexetil, hydroxychloroquine, chloroquine, montelukast sodium, atazanavir, candesartan.
