tetano
Editor, Senior Moderator
Antimicrob Agents Chemother
. 2021 Feb 1;AAC.02577-20.
doi: 10.1128/AAC.02577-20. Online ahead of print.
Kinetic characterization and inhibitor screening for the proteases leading to identification of drugs against SARS-CoV-2
Chih-Jung Kuo[SUP] 1 [/SUP], Tai-Ling Chao[SUP] 2 [/SUP], Han-Chieh Kao[SUP] 2 [/SUP], Ya-Min Tsai[SUP] 2 [/SUP], Yi-Kai Liu[SUP] 1 [/SUP], Lily Hui-Ching Wang[SUP] 3 [/SUP], Ming-Chang Hsieh[SUP] 4 5 [/SUP], Sui-Yuan Chang[SUP] 6 7 [/SUP], Po-Huang Liang[SUP] 8 9 [/SUP]
Affiliations
Abstract
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 (3CL[SUP]pro[/SUP]) and papain-like protease (PL[SUP]pro[/SUP]) 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, 3CL[SUP]pro[/SUP] and PL[SUP]pro[/SUP] 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 3CL[SUP]pro[/SUP] inhibitors and 36 drugs as PL[SUP]pro[/SUP] inhibitors active at 10 μM. Among these inhibitors, 6 drugs were found suppressing SARS-CoV-2 with EC[SUB]50[/SUB] 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.
. 2021 Feb 1;AAC.02577-20.
doi: 10.1128/AAC.02577-20. Online ahead of print.
Kinetic characterization and inhibitor screening for the proteases leading to identification of drugs against SARS-CoV-2
Chih-Jung Kuo[SUP] 1 [/SUP], Tai-Ling Chao[SUP] 2 [/SUP], Han-Chieh Kao[SUP] 2 [/SUP], Ya-Min Tsai[SUP] 2 [/SUP], Yi-Kai Liu[SUP] 1 [/SUP], Lily Hui-Ching Wang[SUP] 3 [/SUP], Ming-Chang Hsieh[SUP] 4 5 [/SUP], Sui-Yuan Chang[SUP] 6 7 [/SUP], Po-Huang Liang[SUP] 8 9 [/SUP]
Affiliations
- PMID: 33526482
- DOI: 10.1128/AAC.02577-20
Abstract
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 (3CL[SUP]pro[/SUP]) and papain-like protease (PL[SUP]pro[/SUP]) 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, 3CL[SUP]pro[/SUP] and PL[SUP]pro[/SUP] 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 3CL[SUP]pro[/SUP] inhibitors and 36 drugs as PL[SUP]pro[/SUP] inhibitors active at 10 μM. Among these inhibitors, 6 drugs were found suppressing SARS-CoV-2 with EC[SUB]50[/SUB] 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.