IN SILICO ANALYSIS OF NOVEL COMPOUNDS TARGETING THE SARS-COV-2 PAPAIN-LIKE PROTEASE

Objective: The present study aimed to design and computationally evaluate pyrimidine-based ring derivatives as potential inhibitors of SARS-CoV-2 papain-like protease (PLpro). Methods: To find the binding affinity between designed compounds and papain-like protease (PLpro) was used molecular docking. Binding free energy and complex stability were verified using molecular mechanics–generalized born surface area (MM-GBSA) simulations. Additionally, the QikProp tool was used to estimate the absorption, distribution, metabolism, and excretion (ADME) characteristics of substances. Results: Docking analysis showed that compound 2 had a glide score of -5.31 kcal/mol, comparable to the co-crystal (-2.10 kcal/mol). Key interactions with Ile548, Ser549, Ala550, Arg836, Asp833 and Ser814 contributed to its stability. Binding free energy analysis revealed that compound 2 (-74.24 kcal/mol). Conclusion: Compound 2 demonstrated potential interactions with papain-like protease (PLpro), comparable to the co-crystal. These findings suggest that compound 2 is a promising lead candidate for SARS-CoV-2 (PLpro)-targeted therapy, warranting further preclinical and biological validation