In-silico Repurposing of Approved Drugs Targeting SARS-CoV-2 Main Protease: A Multidimensional Computational Approach

The primary SARS-CoV-2 protease (Mpro or 3C-like protease) is a functional polypeptide essential for viral multiplication, making it an ideal target for therapeutic development. Given the established safety profiles and production infrastructure of authorized drugs, drug repurposing offers a rapid route to identifying potential treatment options. A prospective computational repurposing approach was employed to identify potential SARS-CoV-2 treatments. The three-dimensional structure (PDB ID: 6LU7) was used, and PLIP was applied to define the active site for ligand binding. iGEMDOCK v. 2.0 facilitated the docking studies, and the Rasmol viewer was used to visualize binding poses. Out of 63 active ligands, sixteen showed potential in suppressing the protease. Among these, candesartan exhibited the most favorable binding energy at –102.43 kcal/mol. This in-silico investigation provides insights into currently available medications that may be useful against SARS-CoV-2 infection and highlights candidates that should be prioritized for further experimental validation and clinical trials. The study identifies SARS-CoV-2 Mpro as a promising therapeutic target and suggests that existing drugs such as candesartan may interact effectively with the protease's active site. However, these computational findings require extensive wet-lab validation, including in vitro assays and clinical trials, before these compounds can be considered for repurposing against SARS-CoV-2 infection.