Drug repurposing and polypharmacology to fight SARS-CoV-2 through the inhibition of the main protease
Luca Pinzi, Annachiara Tinivella, Fabiana Caporuscio, Giulio Rastelli · 2020
Abstract There is an urgent need to develop therapeutic options to fight the outbreak of a novel Coronavirus (SARS-CoV-2), which causes a disease named COVID-19 and is spreading rapidly around the world. Drug repurposing can significantly accelerate the identification of drug candidates suitable for clinical evaluation. Moreover, drugs with polypharmacological effects may increase antiviral activity and/or counteract severe disease complications concurrently affecting COVID-19 patients. Herein, we present the results of a computational drug repurposing campaign in search for potential inhibitors of the main protease of SARS-CoV-2. To this aim, the complete DrugBank database, including drug metabolites, was docked to the recently solved crystal structure of the SARS-CoV-2 Mpro and the results were post-processed by using our in-house tool BEAR. Here we report 32 promising drugs that could be repositioned to fight SARS-CoV-2. Some of them have already entered clinical trials against COVID-19, thus supporting our results, but the vast majority of the selected compounds is new and has never been considered before. For each repurposed compound its therapeutic relevance and the potential beneficial polypharmacological effects that may arise thanks to its original therapeutic indication are thoroughly discussed.