Al-Qattan, M. (2026). Docking, Molecular Dynamics and MMPBSA Study of Selected FDA-Approved Drugs Against SARS-CoV-2 Proteases and Spike Proteins. , 23(1), 12-23. doi: 10.33899/iraqij.p.2025.166836.1176
Mohammed Nooraldeen Al-Qattan. "Docking, Molecular Dynamics and MMPBSA Study of Selected FDA-Approved Drugs Against SARS-CoV-2 Proteases and Spike Proteins". , 23, 1, 2026, 12-23. doi: 10.33899/iraqij.p.2025.166836.1176
Al-Qattan, M. (2026). 'Docking, Molecular Dynamics and MMPBSA Study of Selected FDA-Approved Drugs Against SARS-CoV-2 Proteases and Spike Proteins', , 23(1), pp. 12-23. doi: 10.33899/iraqij.p.2025.166836.1176
Al-Qattan, M. Docking, Molecular Dynamics and MMPBSA Study of Selected FDA-Approved Drugs Against SARS-CoV-2 Proteases and Spike Proteins. , 2026; 23(1): 12-23. doi: 10.33899/iraqij.p.2025.166836.1176

Docking, Molecular Dynamics and MMPBSA Study of Selected FDA-Approved Drugs Against SARS-CoV-2 Proteases and Spike Proteins

Iraqi Journal of Pharmacy
Article 2, Volume 23, Issue 1, March 2026, Pages 12-23    PDF (682.38 K)
Document Type: Research Paper
DOI: 10.33899/iraqij.p.2025.166836.1176
Author
Mohammed Nooraldeen Al-Qattan*
Department of Pharmaceutical Chemistry, College of Pharmacy, Ninevah University, Mosul, Iraq
Abstract
Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rapidly evolved into a global health emergency. Despite extensive research efforts, the lack of fully effective and specific antiviral therapies during the early stages of the pandemic highlighted the urgent need for alternative therapeutic strategies. Drug repurposing has therefore gained attention as a rapid and cost-effective approach to identify potential antiviral agents from existing FDA-approved drugs. Aim: This study aimed to identify promising repurposable FDA-approved drugs with potential inhibitory activity against key SARS-CoV-2 proteins using an integrated computational approach. Methods: A total of 28 FDA-approved drugs were computationally screened against three critical SARS-CoV-2 targets: the papain-like protease, main protease, and spike protein. Molecular docking was performed, followed by binding-site optimization and binding free energy estimation using the MM-GBSA method. Based on docking performance, the top eleven compounds were further evaluated using molecular dynamics (MD) simulations to assess the stability of ligand–protein complexes. Binding free energies were recalculated using the MM-PBSA approach. Results: Initial docking and MM-GBSA analyses identified hydroxychloroquine, rifampicin, ambroxol, chlorpromazine, clarithromycin, ranitidine, and ofloxacin as high-scoring candidates against SARS-CoV-2 targets. Subsequent MD simulations demonstrated stable binding interactions for ambroxol, rifampicin, famotidine, ranitidine, oseltamivir, ofloxacin, and ciprofloxacin. These compounds exhibited favorable binding free energies and maintained structural stability throughout the simulation period. Conclusion: The integrated in silico workflow identified several FDA-approved drugs with stable and energetically favorable interactions with key SARS-CoV-2 proteins. These findings support the potential repurposing of selected compounds, particularly ambroxol and rifampicin, as candidate antiviral agents against SARS-CoV-2. Further experimental validation and clinical investigation are warranted to confirm their therapeutic efficacy.
Keywords
Covid-19; Protease; Spike; Molecular docking; Dynamics; MMGBSA; MMPBSA
Supplementary Files
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