Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies

Sakshi Piplani, Puneet Kumar Singh, David A. Winkler, Nikolai Petrovsky

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
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Abstract

Repurposing of existing drugs and drug candidates is an ideal approach to identify new potential therapies for SARS-CoV-2 that can be tested without delay in human trials of infected patients. Here we applied a virtual screening approach using Autodock Vina and molecular dynamics simulation in tandem to calculate binding energies for repurposed drugs against the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We thereby identified 80 promising compounds with potential activity against SARS-Cov2, consisting of a mixture of antiviral drugs, natural products and drugs with diverse modes of action. A substantial proportion of the top 80 compounds identified in this study had been shown by others to have SARS-CoV-2 antiviral effects in vitro or in vivo, thereby validating our approach. Amongst our top hits not previously reported to have SARS-CoV-2 activity, were eribulin, a macrocyclic ketone analogue of the marine compound halichondrin B and an anticancer drug, the AXL receptor tyrosine kinase inhibitor bemcentinib. Our top hits from our RdRp drug screen may not only have utility in treating COVID-19 but may provide a useful starting point for therapeutics against other coronaviruses. Hence, our modelling approach successfully identified multiple drugs with potential activity against SARS-CoV-2 RdRp.

Original languageEnglish
Article number28
Number of pages12
JournalMolecular Biomedicine
Volume2
Issue number1
DOIs
Publication statusPublished - 20 Sept 2021

Keywords

  • Drug repurposing
  • Molecular docking
  • Molecular dynamics
  • RNA-dependent RNA polymerase
  • SARS-CoV-2

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