In-silico Insights into Protein Targets: New Avenues for Treating E. faecalis in Endodontic Infections – A Systematic Review

Enterococcus faecalis is a key pathogen in persistent endodontic infections, known for its resilience and resistance to conventional treatments. This systematic review (PROSPERO CRD42024610795) explores in silico methodologies targeting E. faecalis proteins to identify novel therapeutic approaches. A comprehensive literature search identified 11 relevant studies employing molecular docking tools such as AutoDock Vina, Glide XP, and SwissDock to investigate interactions between ligands and critical protein targets, including Sortase A, MurA, c-di-AMP synthetase, and quorum sensing regulators. Promising inhibitors, such as pinocembrin, 24-propylcholesterol, and embelin, exhibited potential to disrupt biofilm formation, quorum sensing, and bacterial metabolism. These findings highlight the potential of plant-derived compounds and novel antibacterial agents in addressing E. faecalis -associated infections. While most studies validated computational results with in vitro assays, variability in ligand preparation, protein optimization, and docking methodologies indicates the need for standardization. This review underscores the significant promise of computer-aided drug design (CADD) in developing effective treatments for E. faecalis infections. Integrating in silico and in vitro approaches can accelerate drug discovery, but further in vivo studies are essential to confirm therapeutic potential and facilitate clinical application.