Repurposing of Relatively Large Drugs for the Receptor Binding Domain of SARS-CoV-2 Spike Protein

Nowadays, there are a few therapeutics to prevent or treat COVID-19. Because the development of safe and effective drugs is expensive and time-consuming, drug repurposing is now part of the arsenal of drug discovery. Herein, we focus on the repurposing of relatively large FDA-approved drugs (MW > 500, LogP ≤ 5) that target the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We performed a computational study incorporating molecular docking, molecular dynamics simulations, and relative binding energy calculations to discover prospective compounds with high affinity towards the viral RBD. We found that the most promising drugs, namely, Atazanavir, Zazole, Valrubicin, and Telotristat, influence hotspot residues of the RBD protein and may interfere with the human angiotensin-converting enzyme-2 (ACE2) receptor. Our findings corroborate with the present literature and can accelerate the rational design of selective inhibitors against SARS-CoV-2.