In Silico Destructive Activity of Phytochemicals From Ocimum sanctum Against the T9SS Proteins of Porphyromonas gingivalis.

Periodontitis is a chronic inflammatory condition closely associated with the pathogenic activity of Porphyromonas gingivalis (P. gingivalis). Among its virulence components, the PorA and PorE proteins play essential roles in the type IX secretion system (T9SS), facilitating the release of gingipain-related factors that contribute to tissue destruction. Targeting these proteins may offer a promising therapeutic strategy. This study employed a molecular docking approach to evaluate phytocompounds from Ocimum sanctum (Tulsi) as potential antibacterial lead molecules against PorA and PorE. Ten Tulsi-derived compounds were chosen as ligands, and their binding affinities were compared with those of standard antibiotics, penicillin G, metronidazole, and doxycycline, using the Maestro module of the Schrödinger suite (v2023-2, Schrödinger, Inc., New York City, NY, USA). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation was conducted using SwissADME (Molecular Modelling Group of the SIB Swiss Institute of Bioinformatics and the University of Lausanne, Lausanne, Switzerland), and protein-ligand interactions were visualized to determine molecular compatibility. Among the studied compounds, four (rosmarinic acid, eugenol, penicillin G, and metronidazole) showed inhibitory potential against PorE, while two (rosmarinic acid and penicillin G) demonstrated activity against PorA. Rosmarinic acid displayed the most favorable docking profile, with the highest binding energies for both PorA (ΔG = -3.501 kcal/mol) and PorE (ΔG = -5.728 kcal/mol), outperforming the reference antibiotics and the remaining phytochemicals. These results indicate that rosmarinic acid exhibits strong in silico potential to interfere with T9SS function by targeting PorA and PorE. The compound merits further investigation through in vitro and ex vivo studies as a promising natural inhibitor for managing pathogenic periodontal biofilms and disrupting T9SS-mediated virulence.