In-silico Docking Analysis of Lupeol against the Enterococcal Surface Protein Receptor of Enterococcus faecalis: A Phytoendodontic Approach for Biofilm Disruption

Introduction: Persistent root canal infections often involve Enterococcus faecalis, a biofilm-forming pathogen resistant to conventional irrigants like sodium hypochlorite and Chlorhexidine (CHX). The Enterococcal Surface Protein (Esp) is a key virulence factor facilitating adhesion and biofilm development. Natural compounds like lupeol, derived from Tinospora cordifolia, have shown antimicrobial properties, but their specific interactions with bacterial virulence proteins remain underexplored. Aim: To evaluate the binding affinity and molecular interaction of lupeol with the Esp receptor using in-silico docking, and compare it with CHX, a traditionally used endodontic irrigant. Materials and Methods: The present in-silico docking study was performed using the Esp crystal structure (PDB ID: 6ORI) in the Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospitals (SIMATS, Chennai, India). The protein and ligands were prepared and energy-minimised in AutoDockTools 1.5.6. Lupeol (PubChem CID: 259846) and CHX (PubChem CID: 9552079) were docked at the Esp active site with exhaustiveness set at 8. Binding affinities (kcal/mol) and key interactions were analysed. Results: Lupeol exhibited a strong binding affinity of -9.14 kcal/ mol, interacting specifically with the Histidine (HIS) residue of the Esp receptor. In comparison, CHX demonstrated a higher binding affinity (-11.83 kcal/mol) with multiple interactions involving Tyrosine (TYR), Phenylalanine (PHE), Methionine (MET), Leucine (LEU), Arginine (ARG), and Glutamic Acid (GLU), residues. Despite a narrower interaction profile, lupeol’s targeted engagement and favourable binding energy suggest its potential as a natural Esp inhibitor. Conclusion: Lupeol demonstrated promising molecular interaction with the E. faecalis Esp receptor, indicating its potential as a natural, target-specific anti-biofilm agent. These findings support further experimental validation and highlight the relevance of phytoendodontics and in-silico methods in the discovery of safe and effective alternatives to synthetic irrigants.