Combinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput ScreeningCombinatorial Chemistry & High Throughput Screening1386-20731875-5402Bentham Science64448710.2174/1386207325666220816125639ChemistryResearch ArticleEvaluations of FDA-approved Drugs Targeting 3CLP of SARS-CoV-2 Employing a Repurposing StrategyAhmadSyedinfo@benthamscience.netKhalidMohammadinfo@benthamscience.netDepartment of Medical Biotechnology,, Yeungnam UniversityCollege of Pharmacy,Department of Pharmacognosy,, Prince Sattam Bin Abdul Aziz University0110202427192805281507012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjpbr.com/1386-2073/article/view/644487

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.

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