IN SILICO EVALUATION OF SARS-COV-2 PAPAIN-LIKE PROTEASE INHIBITORY ACTIVITY OF SOME FDA-APPROVED DRUGS

Abstract

Objective: In this study, it was aimed to perform in silico studies on the papain-like protease structure of SARS-CoV-2 (PDB: 7JIT) of 1300 FDA-approved drugs downloaded from the ZINC database. Material and Method: A molecular docking study was performed with PLpro (PDB ID: 7JIT) using four different molecular docking programs for a total of 1300 FDA-approved drugs obtained from the ZINC database. Conivaptan and amphotericin B were obtained in docking analysis with AutoDock Vina and Sybyl-X, respectively. Docking analysis with Glide SP and Glide XP resulted in fludarabine and panobinostat, respectively. Molecular dynamics simulations were performed for a period of 120 ns to check the stability of these four drugs. Result and Discussion: The reliability of the results obtained using four different molecular docking programs on the SARS-CoV-2 papain-like protease of 1300 drug molecules was checked by reinserting the co-crystal ligand. Protein-ligand interactions between fludarabine, conivaptan, amphotericin-B, panobinostat, and PLpro were given. In the molecular dynamics study, RMSD, RMSF, Rg, and SASA analyses were performed for four systems. It was observed that RMSD remained constant for all 120 ns for all four systems except for amphotericin B, which deviated slightly towards the end of 120 ns. No significant fluctuation was noticed in the RMSF graphics for all four systems.