Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV

SAR QSAR Environ Res. 2020 Nov;31(11):857-867. doi: 10.1080/1062936X.2020.1825014.


A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has resulted in an increasing number of patients globally, and has become a highly lethal pathogenic member of the coronavirus family affecting humans. 2019-nCoV has established itself as one of the most threatening pandemics that human beings have faced, and therefore analysis and evaluation of all possible responses against infection is required. One such strategy includes utilizing the knowledge gained from the SARS and MERS outbreaks regarding existing antivirals. Indicating a potential for success, one of the drugs, remdesivir, under repurposing studies, has shown positive results in initial clinical studies. Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database. Further clustering on the basis of structural features and scoring refinement was performed to filter out false positive hits. Finally, molecular dynamics simulation was carried out to validate the identification of hits as RdRp inhibitors against novel coronavirus 2019-nCoV. The results yielded two putative hits which can inhibit RdRp with better potency than remdesivir, subject to further biological evaluation.

Keywords: COVID-19; Remdesivir–RdRp complex; molecular docking; molecular dynamics; scoring refinement.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / chemistry
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives*
  • Alanine / chemistry
  • Alanine / pharmacology
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Betacoronavirus / drug effects
  • Betacoronavirus / enzymology
  • COVID-19
  • Coronavirus Infections / drug therapy
  • Molecular Docking Simulation*
  • Pandemics
  • Pneumonia, Viral
  • Quantitative Structure-Activity Relationship
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • SARS-CoV-2
  • Viral Proteins / drug effects


  • Antiviral Agents
  • Viral Proteins
  • remdesivir
  • Adenosine Monophosphate
  • RNA-Dependent RNA Polymerase
  • Alanine

Supplementary concepts

  • COVID-19 drug treatment