Virtual Screening of Bacteriocins From Lactic Acid Bacteria Against Monkeypox DNA Polymerase: Sakacin P and Mundticin KS Emerge as Promising Candidates

Abstract

ABSTRACT The monkeypox virus (MPXV) has recently risen to be a significant global health threat and currently there are no approved antiviral agents, which makes it necessary to develop new antiviral strategies. In this study, we employed in silico techniques to investigate whether bacteriocins could be potent inhibitors of the MPXV DNA polymerase (MPDP). At first, the MPXV DNA polymerase enzyme chain was extracted from the Cryo‐EM structure of MPXV DNA replication complex and was then assessed using SWISS‐MODEL/QMEAN for structural quality. The structures of selected bacteriocins were either retrieved from the Protein Data Bank or predicted using AlphaFold. The quality of these predicted models was measured by LGscore. Moreover, the physicochemical properties of the selected bacteriocins, such as Sakacin P and Mundticin KS, were analyzed to assess their molecular stability and compatibility with the molecular docking process. The results of protein‐peptide docking simulations on the HADDOCK platform showed that among all the bacteriocins tested, Sakacin P and Mundticin KS had the highest binding affinities toward MPXV DNA polymerase. The analysis of the docking experiments also revealed vital stabilizing interactions, such as the formation of hydrogen bonds, ionic linkages, and π–π stacking, which were crucial in the strength of the protein–ligand complexes. Subsequently, the molecular dynamics (MD) simulations further confirmed the stability of the protein–bacteriocin complexes. Our results indicate that bacteriocins, especially Sakacin P and Mundticin KS, can be considered potential antiviral agents against MPXV by interfering with its DNA replication mechanism. The present work shall serve as a reference for future laboratory testing and for the promising innovation of bacteriocin‐based drugs targeting MPXV.