Virtual screening of bacteriocins from lactic acid bacteria against Monkeypox DNA Polymerase: Sakacin-P is a potent DNA polymerase inhibitor

Monkeypox virus (MPXV) has emerged as a significant global health concern, necessitating the development of novel antiviral strategies. In this study, we employed an in silico approaches to investigate the potential of bacteriocins as inhibitors of the MPXV DNA polymerase (MPDP). Initially, protein structure modeling was performed using SWISS-MODEL, and the quality of the generated models was evaluated based on LGscore. The physicochemical properties of selected bacteriocins, including Sakacin-P and Mundticin-KS, were assessed to determine their stability and suitability for molecular docking. Protein-peptide docking simulations using the HADDOCK platform revealed that Sakacin-P exhibited a higher binding affinity for the MPXV DNA polymerase. The docking analysis indicated the presence of strong hydrogen bonds, ionic interactions, and π-π stacking interactions, which contributed to the stability of the protein-ligand complex. Molecular dynamics (MD) simulations further validated the stability of the docked complex by analyzing root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), H-bond and Van der Waals interactions, and solvent-accessible surface area (SASA). Our findings suggest that bacteriocins, particularly Sakacin-P, have promising antiviral properties against MPXV by targeting its DNA replication complex. This study provides a foundation for further experimental validation and the potential development of bacteriocin-based therapeutics against MPXV.