tetano
Editor, Senior Moderator
Pharmaceutics
. 2022 Jan 12;14(1):176.
doi: 10.3390/pharmaceutics14010176.
Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets
Pei-Chen Yu[SUP] 1 [/SUP], Chen-Hao Huang[SUP] 2 [/SUP], Chih-Jung Kuo[SUP] 3 [/SUP], Po-Huang Liang[SUP] 4 5 [/SUP], Lily Hui-Ching Wang[SUP] 6 [/SUP], Max Yu-Chen Pan[SUP] 6 [/SUP], Sui-Yuan Chang[SUP] 7 8 [/SUP], Tai-Ling Chao[SUP] 7 9 [/SUP], Si-Man Ieong[SUP] 7 [/SUP], Jun-Tung Fang[SUP] 7 [/SUP], Hsuan-Cheng Huang[SUP] 10 [/SUP], Hsueh-Fen Juan[SUP] 1 2 11 [/SUP]
Affiliations
Abstract
Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PL[SUP]pro[/SUP]), and 3C-like protease (3CL[SUP]pro[/SUP]) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.
Keywords: 3C-like protease (3CLpro/Mpro); docking simulation; papain-like protease (PLpro); severe acute respiratory syndrome coronavirus 2; tamoxifen; transmembrane protease serine 2 (TMPRSS2).
. 2022 Jan 12;14(1):176.
doi: 10.3390/pharmaceutics14010176.
Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets
Pei-Chen Yu[SUP] 1 [/SUP], Chen-Hao Huang[SUP] 2 [/SUP], Chih-Jung Kuo[SUP] 3 [/SUP], Po-Huang Liang[SUP] 4 5 [/SUP], Lily Hui-Ching Wang[SUP] 6 [/SUP], Max Yu-Chen Pan[SUP] 6 [/SUP], Sui-Yuan Chang[SUP] 7 8 [/SUP], Tai-Ling Chao[SUP] 7 9 [/SUP], Si-Man Ieong[SUP] 7 [/SUP], Jun-Tung Fang[SUP] 7 [/SUP], Hsuan-Cheng Huang[SUP] 10 [/SUP], Hsueh-Fen Juan[SUP] 1 2 11 [/SUP]
Affiliations
- PMID: 35057070
- DOI: 10.3390/pharmaceutics14010176
Abstract
Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PL[SUP]pro[/SUP]), and 3C-like protease (3CL[SUP]pro[/SUP]) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.
Keywords: 3C-like protease (3CLpro/Mpro); docking simulation; papain-like protease (PLpro); severe acute respiratory syndrome coronavirus 2; tamoxifen; transmembrane protease serine 2 (TMPRSS2).