Identification of Potential Inhibitors of SARS-CoV-2 Main Protease Via a Rapid In-Silico Drug Repurposing Approach

Anin-silico drug repurposing study was carried out to search forpotential COVID-19 antiviral agents. A dataset of 1615 FDA-approveddrugs was docked in the active site of SARS CoV-2 Main protease. Asubset of the top scoring hit compounds was subjected to follow-upmolecular dynamics simulations to further characterise the predictedbinding modes. The main findings are that the drugs Aliskiren,Capreomycin, Isovuconazonium, emerge as novel potential inhibitors.We also observed that Ceftolozane, Cobicistat, Carfilzomib andSaquinavir are well-ranked by our protocol, in agreement with otherrecent in silico drug repurposing studies, however MD simulationsshows only potential for the three first, as Saquinavir exhibited anunstable binding mode. As many HIV-protease inhibitors has beenreported as active and not active, Atazanavir and Lopinavir wereincluded in the data set in order to rationalize the findings. Inaddition, our protocol ranked favourably Dronedarone suggesting thatthis recently reported SARS-CoV-2 inhibitor targets SARS-CoV-2 Mainprotease.