Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets
Journal
Pharmaceutics
Journal Volume
14
Journal Issue
1
Pages
176
Date Issued
2022-01-12
Author(s)
Yu, Pei-Chen
Huang, Chen-Hao
Kuo, Chih-Jung
Liang, Po-Huang
Wang, Lily Hui-Ching
Pan, Max Yu-Chen
Ieong, Si-Man
Fang, Jun-Tung
Huang, Hsuan-Cheng
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 (PLpro), and 3C-like protease (3CLpro) 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.
Subjects
3C-like protease (3CLpro/Mpro); docking simulation; papain-like protease (PLpro); severe acute respiratory syndrome coronavirus 2; tamoxifen; transmembrane protease serine 2 (TMPRSS2)
SDGs
Publisher
MDPI
Type
journal article