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. Supplementary Information The online version contains supplementary material available at 10.1186/s43556-021-00050-3.
【저자키워드】 Drug repurposing, SARS-CoV-2, molecular docking, molecular dynamics, RNA-dependent RNA polymerase, 【초록키워드】 Trial, antiviral drugs, repurposing, Virtual screening, drug, in vitro, binding energy, Molecular dynamics simulation, Antiviral effect, Repurposed drug, RdRP, receptor, in vivo, inhibitor, utility, SARS-CoV-2 RdRp, tyrosine, starting point, AutoDock vina, supplementary material, infected patients, other coronaviruses, Compound, treating COVID-19, drug candidate, anticancer, potential therapy, approach, shown, tested, identify, proportion, reported, applied, calculate, the SARS-CoV-2, 【제목키워드】 COVID-19, therapy, RNA, Repurposed drug, RNA polymerase,