20210201 Liang PH Epub

Kinetic characterization and inhibitor screening for the proteases leading to identification of drugs against SARS-CoV-2

Kinetic characterization and inhibitor screening for the proteases leading to identification of drugs against SARS-CoV-2

Antimicrob Agents Chemother. 2021 Mar 18; 65(4):e02577-20. Print 2021 Mar 18.
doi: 10.1128/AAC.02577-20

閱讀文章

Kuo CJ, Chao TL, Kao HC, Tsai YM, Liu YK, Wang LH, Hsieh MC, Chang SY, Liang PH

摘要

The coronavirus (CoV) disease (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has claimed many lives worldwide and is still spreading since December 2019. The 3C-like protease (3CLpro) and papain-like protease (PLpro) are essential for maturation of viral polyproteins in SARS-CoV-2 life cycle and thus regarded as key drug targets for the disease. In this study, 3CLpro and PLpro assay platforms were established and their substrate specificities were characterized. The assays were used to screen collections of 1068 and 2701 FDA-approved drugs. After excluding the externally used drugs which are too toxic, we totally identified 12 drugs as 3CLpro inhibitors and 36 drugs as PLpro inhibitors active at 10 μM. Among these inhibitors, 6 drugs were found suppressing SARS-CoV-2 with EC50 below or close to 10 μM. This study enhances our understanding on the proteases and provides FDA approved drugs for prevention and/or treatment of COVID-19.