Repurposing antiviral drugs against HTLV-1 protease by molecular docking and molecular dynamics simulation

• Published in: Journal of biomolecular structure & dynamics Vol. 41; no. 11; pp. 5057 - 5066
• Main Authors: Jahantigh, Hamidreza, Ahmadi, Nahid, Lovreglio, Piero, Stufano, Angela, Enayatkhani, Maryam, Shahbazi, Behzad, Ahmadi, Khadijeh
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 24.07.2023
• Subjects: Antiviral Agents - chemistry; Aspartic Acid Endopeptidases - chemistry; Atazanavir Sulfate; Drug Repositioning; drug repurposing; HTLV-1; Humans; molecular docking; Molecular Docking Simulation; molecular dynamics (MD) simulation; Molecular Dynamics Simulation; protease; Protease Inhibitors - chemistry; Saquinavir; Simeprevir; protease; HTLV-1; drug repurposing; molecular docking; molecular dynamics (MD) simulation
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2022.2078411

Human T-cell leukemia virus type I (HTLV-1) belongs to the delta retrovirus family and the etiological agent of adult T-cell leukemia (ATL(. While the current HTLV-1 therapy, relies on using Zidovudine plus IFN-γ, there is no FDA approved drugs against it. In silico drug repurposing is a fast and accurate way for screening US-FDA approved drugs to find a therapeutic option for the HTLV-1 infection. So that, this research aims to analyze a dataset of approved antiviral drugs as a potential prospect for an anti-viral drug against HTLV-1 infection. Molecular docking simulation was performed to identify interactions of the antiviral drugs with the key residues in the HTLV-1 protease binding site. Then, molecular dynamics simulation was also performed for the potential protein-ligand complexes to confirm the stable behavior of the ligands inside the binding pocket. The best docking scores with the target was found to be Simeprevir, Atazanavir, and Saquinavir compounds which indicate that these drugs can firmly bind to the HTLV-1 protease. The MD simulation confirmed the stability of Simeprevir-protease, Atazanavir-Protease, and Saquinavir-Protease interactions. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against HTLV-1 infection. Communicated by Ramaswamy H. Sarma