Repurposing the natural compounds as potential therapeutic agents for COVID-19 based on the molecular docking study of the main protease and the receptor-binding domain of spike protein

J Mol Model. 2022 May 16;28(6):153. doi: 10.1007/s00894-022-05138-3.


Severe acute respiratory syndrome coronavirus (SARS-CoV-2) enters the cell by interacting with the human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of spike (S) protein. In the cell, the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is essential for its life cycle and controls coronavirus replication. Therefore, the S-RBD and 3CLpro are hot targets for drug discovery against SARS-CoV-2. This study was to identify repurposing drugs using in silico screening, docking, and molecular dynamics simulation. The study identified bentiamine, folic acid, benfotiamine, and vitamin B12 against the RBD of S protein and bentiamine, folic acid, fursultiamine, and riboflavin to 3CLpro. The strong and stable binding of these safe and cheap vitamins at the important residues (R403, K417, Y449, Y453, N501, and Y505) in the S-protein-ACE2 interface and 3CLpro binding site residues especially active site residues (His 41 and Cys 145), indicating that they could be valuable repurpose drugs for inhibiting SARS-CoV-2 entry into the host and replication.

Keywords: Coronavirus; Docking; Drug discovery; Main protease; Molecular dynamics; Receptor-binding domain.

MeSH terms

  • Angiotensin-Converting Enzyme 2*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • COVID-19 Drug Treatment*
  • Coronavirus 3C Proteases*
  • Drug Repositioning
  • Folic Acid
  • Humans
  • Molecular Docking Simulation
  • Protein Binding
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus* / metabolism


  • Antiviral Agents
  • Biological Products
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Folic Acid
  • Angiotensin-Converting Enzyme 2
  • 3C-like proteinase, SARS-CoV-2
  • Coronavirus 3C Proteases