A new glimpse on the active site of SARS-CoV-2 3CLpro, coupled with drug repurposing study

Coronavirus disease 2019 (COVID-19) is caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). Its main protease, 3C-like protease (3CLpro), is an attractive target for drug design, due to its importance in virus replication. The analysis of the radial distribution function of 159 3CLpro structures reveals a high similarity index. A study of the catalytic pocket of 3CLpro with bound inhibitors reveals that the influence of the inhibitors is local, perturbing dominantly only residues in the active pocket. A machine learning based model with high predictive ability against SARS-CoV-2 3CLpro is designed and validated. The model is used to perform a drug-repurposing study, with the main aim to identify existing drugs with the highest 3CLpro inhibition power. Among antiviral agents, lopinavir, idoxuridine, paritaprevir, and favipiravir showed the highest inhibition potential. Graphical abstract Enzyme – ligand interactions as a key ingredient for successful drug design