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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.<\/jats:p>","DOI":"10.1186\/s43556-021-00050-3","type":"journal-article","created":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T23:04:16Z","timestamp":1632092656000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies"],"prefix":"10.1186","volume":"2","author":[{"given":"Sakshi","family":"Piplani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puneet Kumar","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-6076","authenticated-orcid":false,"given":"David A.","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-5245","authenticated-orcid":false,"given":"Nikolai","family":"Petrovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"issue":"6497","key":"50_CR1","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1126\/science.abb4489","volume":"368","author":"W Dai","year":"2020","unstructured":"Dai W, Zhang B, Jiang XM, Su H, Li J, Zhao Y, et al. 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