Title:Evaluations of FDA-approved Drugs Targeting 3CLP of SARS-CoV-2 Employing a Repurposing Strategy
Volume: 27
Issue: 19
Author(s): Syed Sayeed Ahmad*Mohammad Khalid
Affiliation:
- Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea
Keywords:
Virtual screening, molecular docking, MD simulation, drug re-purposing, COVID-19, 3CLP.
Abstract:
Background: The SARS-CoV-2 coronavirus (COVID-19) has raised innumerable global
concerns, and few effective treatment strategies have 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.
Methods: In this study, we performed structure-based virtual screening of FDA drugs approved
during 2015-2019 (a total of 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 the 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.
Results: Accordingly, we suggest cefiderocol might be effective against SARS-CoV-2 and urge
that experimental validation be performed to determine the antiviral efficacy of cefiderocol against
SARS-CoV-2.
Discussion: Along with these, cefiderocol is effective for treating respiratory tract pathogens and a
wide range of gram-negative bacteria for whom there are limited therapeutic alternatives.
Conclusion: This article aimed to explore the FDA-approved drugs as a repurposing study against
3CLP for COVID-19 management.