Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets

Pei Chen Yu, Chen Hao Huang, Chih Jung Kuo, Po Huang Liang, Lily Hui Ching Wang, Max Yu Chen Pan, Sui Yuan Chang, Tai Ling Chao, Si Man Ieong, Jun Tung Fang, Hsuan Cheng Huang*, Hsueh Fen Juan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number176
JournalPharmaceutics
Volume14
Issue number1
DOIs
StatePublished - Jan 2022

Keywords

  • 3C-like protease (3CL/M)
  • Docking simulation
  • Papain-like protease (PL)
  • Severe acute respiratory syndrome coronavirus 2
  • Tamoxifen
  • Transmembrane protease serine 2 (TMPRSS2)

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