Towards Screening and Repurposing of Approved Drugs for the Treatment of COVID-19 Using Molecular Docking

Abstract

Molecular docking was applied to investigate interactions between 1638 approved drugs, SARS-CoV-2 virus proteins (spike, nonstructural proteins NSP3, NSP7, NSP8, NSP9, NSP10, NSP12, NSP15, NSP16, and NSP10-NSP16 complex), and the human angiotensinconverting enzyme 2 (ACE2) protein and its Spike@ACE2 complex. Structures of these approved drugs were fully optimized using the universal force field (UFF), and their lowest energy conformations were used for docking on the (co)crystallized structures of the target proteins taken from the protein data bank (PDB). The docking procedure was performed in two stages, and the results were evaluated based on four docking scores (ranking indices), which were used to measure the comparative affinities of the studied drugs towards the SARSCoV-2 virus proteins. Details of the positions, orientations, and interactions of the first three highest-ranked drugs in the binding pocket of the COVID-19 spike, NSP7, and human ACE2 proteins (as representatives) were visualized and analyzed. Based on the results of this molecular docking study, vazegepant, dasabuvir, vitamin E, fosamprenavir, raltegravir, canagliflozin, biliverdin, and imatinib drugs can be considered promising for further molecular mechanics/dynamics simulations and clinical studies to improve the screening process © 2023, Physical Chemistry Research. All Rights Reserved.