Structure-Based Drug Repurposing Through Molecular Docking and ADMET Profiling of FDA-Approved Drugs Targeting SARS-CoV-2 Main Protease (Mpro)

Rathnayaka Mudiyanselage Isuru Gayashan Wijiesinghe

Abstract: The emergence of Coronavirus Disease 2019 (COVID-19) created an unprecedented global healthcare crisis, emphasizing the urgent need for rapid therapeutic development. Conventional drug discovery pipelines are time-consuming and resource intensive. This made drug repurposing a practical option during health crises. SARS-CoV-2 main protease (Mpro) plays a critical role in viral replication and transcription and is considered a prime therapeutic target due to its absence in human host cells. This study aimed to identify potential SARS-CoV-2 Mpro inhibitors through structure-based molecular docking of FDA-approved drugs, combined with in-silico pharmacokinetic and toxicity evaluation. The crystal structure of Mpro was retrieved from the Protein Data Bank, and a curated library of approved drugs was obtained from public databases. Molecular docking was performed using AutoDock Vina, and protein?ligand interactions were analyzed using Discovery Studio Visualizer. Drug-likeness and pharmacokinetics were assessed using SwissADME and pkCSM. Docking analysis identified several approved drugs with strong binding affinities ranging from ?8.5 to ?11.2 kcal/mol, surpassing known reference inhibitors. Key hydrogen bonding and hydrophobic interactions were observed with catalytic residues His41 and Cys145, indicating stable binding within the active site. ADMET profiling demonstrated favorable oral bioavailability, acceptable metabolic stability, and low predicted toxicity for selected lead compounds. The results suggest that multiple FDA-approved drugs exhibit promising inhibitory potential against SARS-CoV-2 Mpro and may be considered for further experimental validation. This study highlights the effectiveness of computational drug repurposing strategies in accelerating therapeutic discovery during pandemics while minimizing development cost and time.

Keywords: SARS-CoV-2, drug repurposing, molecular docking, Mpro, ADMET, COVID-19 therapeutics

How to Cite?: Rathnayaka Mudiyanselage Isuru Gayashan Wijiesinghe, "Structure-Based Drug Repurposing Through Molecular Docking and ADMET Profiling of FDA-Approved Drugs Targeting SARS-CoV-2 Main Protease (Mpro)", Volume 15 Issue 2, February 2026, International Journal of Science and Research (IJSR), Pages: 204-207, https://www.ijsr.net/getabstract.php?paperid=SR26201102349, DOI: https://dx.doi.org/10.21275/SR26201102349