Evaluations of FDA-approved drugs targeting 3CLP of SARS-CoV-2 employing a repurposing strategy.

Abstract

The SARS-CoV-2 coronavirus (COVID-19) has raised innumerable global concerns, and few effective treatment strategy has yet been permitted by the FDA to lighten the disease burden. SARS-CoV-2 3C-like proteinase (3CLP) is a crucial protease and plays a key role in the viral life cycle, as it controls replication, and thus, it is viewed as a target for drug design. In this study, we performed structure-based virtual screening of FDA drugs approved during the period 2015-2019 (total 220 drugs) for interaction with the active site of 3CLP (PDB ID 6LU7) using AutoDock 4.2. We report the top ten drugs that outperform the reported drugs against 3CLP (Elbasvir and Nelfinavir), particularly Cefiderocol having the highest affinity among the compounds tested, with a binding energy of -9.97 kcal/mol. H-bond (LYS102:HZ2-ligand:O49), hydrophobic (ligand-VAL104), and electrostatic (LYS102:NZ-ligand:O50) interactions were observed in cefiderocol-3CLP complex. The docked complex was subjected to a 50 ns molecular dynamics study to check its stability, and stable RMSD and RMSF graphs were observed. Accordingly, we suggest cefiderocol might be effective against SARS-CoV-2 and urge that experimental validation to be performed to determine the antiviral efficacy of cefiderocol against SARS-CoV-2. Along with these, cefiderocol is effective for the treatment of respiratory tract pathogens and wide range of gram-negative bacteria for whom there are limited therapeutic alternatives. The aim of this article was to explore the FDA approved drugs as repurposing study against 3CLP for COVID-19 management.