In silico screening of known small molecules to bind ACE2 specific RBD on Spike glycoprotein of SARS-CoV-2 for repurposing against COVID-19

F1000Res. 2020 Jul 1:9:663. doi: 10.12688/f1000research.24143.1. eCollection 2020.


Background: Human coronavirus (SARS-CoV-2) is causing a pandemic with significant morbidity and mortality. As no effective novel drugs are available currently, drug repurposing is an alternative intervention strategy. Here we present an in silico drug repurposing study that implements successful concepts of computer-aided drug design (CADD) technology for repurposing known drugs to interfere with viral cellular entry via the spike glycoprotein (SARS-CoV-2-S), which mediates host cell entry via the hACE2 receptor. Methods: A total of 4015 known and approved small molecules were screened for interaction with SARS-CoV-2-S through docking studies and 15 lead molecules were shortlisted. Additionally, streptomycin, ciprofloxacin, and glycyrrhizic acid (GA) were selected based on their reported anti-viral activity, safety, availability and affordability. The 18 molecules were subjected to molecular dynamics (MD) simulation. Results: The MD simulation results indicate that GA of plant origin may be repurposed for SARS-CoV-2 intervention, pending further studies. Conclusions: Repurposing is a beneficial strategy for treating COVID-19 with existing drugs. It is aimed at using docking studies to screen molecules for clinical application and investigating their efficacy in inhibiting SARS-CoV-2-S. SARS-CoV-2-S is a key pathogenic protein that mediates pathogen-host interaction. Hence, the molecules screened for inhibitory properties against SARS-CoV-2-S can be clinically used to treat COVID-19 since the safety profile is already known.

Keywords: ACE2; Pathogen host interaction; SARS-CoV-2; SARS-CoV-2-Spike Glycoprotein; Small Molecules.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / drug effects*
  • COVID-19
  • Coronavirus Infections*
  • Drug Design*
  • Drug Repositioning*
  • Humans
  • Molecular Docking Simulation
  • Pandemics*
  • Peptidyl-Dipeptidase A
  • Pneumonia, Viral*
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors*
  • Virus Internalization / drug effects


  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

The study was sponsored by Atrimed Pharmaceuticals Pvt. Ltd and no external funding was received for the study.