Targeting SARS-CoV-2 Main Protease: A Computational Drug Repurposing Study

Arch Med Res. 2021 Jan;52(1):38-47. doi: 10.1016/j.arcmed.2020.09.013. Epub 2020 Sep 17.


Background and aims: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) induced Novel Coronavirus Disease (COVID-19) has currently become pandemic worldwide. Though drugs like remdesivir, favipiravir, and dexamethasone found beneficial for COVID-19 management, they have limitations clinically, and vaccine development takes a long time. The researchers have reported key proteins which could act as druggable targets. Among them, the major protease Mpro is first published, plays a prominent role in viral replication and an attractive drug-target for drug discovery. Hence, to target Mpro and inhibit it, we accomplished the virtual screening of US-FDA approved drugs using well-known drug repurposing approach by computer-aided tools.

Methods: The protein Mpro, PDB-ID 6LU7 was imported to Maestro graphical user interphase of Schrödinger software. The US-FDA approved drug structures are imported from DrugBank and docked after preliminary protein and ligand preparation. The drugs are shortlisted based on the docking scores in the Standard Precision method (SP-docking) and then based on the type of molecular interactions they are studied for molecular dynamics simulations.

Results: The docking and molecular interactions studies, five drugs emerged as potential hits by forming hydrophilic, hydrophobic, electrostatic interactions. The drugs such as arbutin, terbutaline, barnidipine, tipiracil and aprepitant identified as potential hits. Among the drugs, tipiracil and aprepitant interacted with the Mpro consistently, and they turned out to be most promising.

Conclusions: This study shows the possible exploration for drug repurposing using computer-aided docking tools and the potential roles of tipiracil and aprepitant, which can be explored further in the treatment of COVID-19.

Keywords: COVID-19; Docking; In silico; M(pro); Repurposing; SARS-CoV-2.

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases / antagonists & inhibitors*
  • Coronavirus 3C Proteases / chemistry
  • Coronavirus 3C Proteases / metabolism
  • Drug Discovery / methods
  • Drug Repositioning / methods*
  • Humans
  • Molecular Docking Simulation / methods
  • Molecular Dynamics Simulation
  • Molecular Targeted Therapy
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use*
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / enzymology*


  • Antiviral Agents
  • Protease Inhibitors
  • 3C-like protease, SARS coronavirus
  • Coronavirus 3C Proteases