Avicenna Journal of Pharmaceutical Research

en Remdesivir Analogues as Promising SARS-CoV-2 RNA-Dependent RNA Polymerase Inhibitors: A Molecular Docking Study تخصصي Special پژوهشي Research Background: Coronavirus RNA-dependent RNA polymerase (RdRp) is vital for viral replication and serves as a major therapeutic target. During the early stages of the COVID-19 pandemic, remdesivir (RDV), a well-characterized RdRp inhibitor, represented an effective therapeutic agent against SARS-CoV-2 infection. Method: Structurally similar RDV analogues were retrieved from the ZINC, CACTUS, and ChEMBL databases through ligand-based similarity searching. The corresponding triphosphate forms were modeled based on the active remdesivir metabolite, remdesivir triphosphate (RDV-TP), and evaluated by molecular docking against SARS-CoV-2 RdRp using AutoDock Vina implemented in PyRx. Results: Among nucleotide analogues and their corresponding triphosphate forms, compound 2A (5-(7-amino-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-tetrahydro-2-(hydroxymethyl)furan-3-ol) exhibited the most favorable predicted binding affinity in its triphosphate form. Conclusion: These findings suggest that novel nucleotide analogues hold promise as potential drug candidates for the treatment of SARS-CoV-2 infection.   COVID-19, Drug Discovery, Molecular Docking, RdRp, Virtual Screening 99 105 http://ajpr.umsha.ac.ir/browse.php?a_code=A-10-2-90&slc_lang=en&sid=1 Mohadese Mohammadi No Medicinal Chemistry Laboratory, Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran Kimia Rayatsanati No Medicinal Chemistry Laboratory, Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran Mozhgan Zahmatkesh No Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran Parisa Azerang No Medicinal Chemistry Laboratory, Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran Azar Tahghighi atahghighi2009@gmail.com Yes Medicinal Chemistry Laboratory, Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran