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

  • Pharmaceutics. 2022 Jan 12;14(1):176. doi: 10.3390/pharmaceutics14010176.
Pei-Chen Yu  1 ,  Chen-Hao Huang  2 ,  Chih-Jung Kuo  3 ,  Po-Huang Liang  4  5 ,  Lily Hui-Ching Wang  6 ,  Max Yu-Chen Pan  6 ,  Sui-Yuan Chang  7  8 ,  Tai-Ling Chao  7  9 ,  Si-Man Ieong  7 ,  Jun-Tung Fang  7 ,  Hsuan-Cheng Huang  10 ,  Hsueh-Fen Juan  1  2  11
Affiliations
  • 1. Department of Life Science and Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
  • 2. Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.
  • 3. Department of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
  • 4. Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
  • 5. Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, Taiwan.
  • 6. Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30004, Taiwan.
  • 7. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 10048, Taiwan.
  • 8. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
  • 9. Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
  • 10. Institute of Biomedical Informatics, National Yang Ming Chaio Tung University, Taipei 11230, Taiwan.
  • 11. Center for Computational and Systems Biology, National Taiwan University, Taipei 10617, Taiwan.
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 (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.

Keywords
3C-like protease (3CLpro/Mpro); docking simulation; papain-like protease (PLpro); severe acute respiratory syndrome coronavirus 2; tamoxifen; transmembrane protease serine 2 (TMPRSS2).
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