In silico analysis and identification of promising hits against 2019 novel coronavirus 3C-like main protease enzyme

J Biomol Struct Dyn. 2021 Sep;39(14):5290-5303. doi: 10.1080/07391102.2020.1787228. Epub 2020 Jul 1.


The recent outbreak of the 2019 novel coronavirus disease (COVID-19) has been proved as a global threat. No particular drug or vaccine has not yet been discovered which may act specifically against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and causes COVID-19. For this highly infectious virus, 3CL-like main protease (3CLpro) plays a key role in the virus life cycle and can be considered as a pivotal drug target. Structure-based virtual screening of DrugBank database resulted in 20 hits against 3CLpro. Atomistic 100 ns molecular dynamics of five top hits and binding energy calculation analyses were performed for main protease-hit complexes. Among the top five hits, Nafarelin and Icatibant affirmed the binding energy (g_MMPBSA) of -712.94 kJ/mol and -851.74 kJ/mol, respectively. Based on binding energy and stability of protein-ligand complex; the present work reports these two drug-like hits against SARS-CoV-2 main protease.Communicated by Ramaswamy H. Sarma.

Keywords: COVID-19; cobicistat; drug hits; icatibant; main protease enzyme; nafarelin.

MeSH terms

  • COVID-19*
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Peptide Hydrolases
  • Protease Inhibitors / pharmacology
  • SARS-CoV-2*


  • Protease Inhibitors
  • Peptide Hydrolases