Multi-Target Inhibition of Glucan Synthesis and Adhesion in Streptococcus mutans by Clitoria ternatea Flavonoids - An In Silico Study

Abstract

Background: Streptococcus mutans is a primary etiological agent of dental caries, largely due to its ability to adhere to tooth surfaces and synthesize extracellular glucans. Natural flavonoids from Clitoria ternatea have demonstrated antimicrobial and antibiofilm properties; however, their interactions with key cariogenic virulence proteins remain inadequately explored. Aim: To evaluate the anti-virulence potential of quercetin, kaempferol, and myricetin from Clitoria ternatea against Glucosyltransferase B (GtfB) and Adhesin P1 (SpaP) of Streptococcus mutans using computational approaches. Materials and Methods: Three flavonoids were retrieved from the PubChem database and docked against GtfB (PDB ID: 8FG8) and SpaP (PDB ID: 4TSH) using AutoDock Vina. Protein–ligand interactions were analyzed using Discovery Studio Visualizer. Drug-likeness, physicochemical properties, and pharmacokinetic characteristics were assessed using the SwissADME web server. Results: All flavonoids demonstrated favorable binding affinities toward both virulence proteins. Quercetin exhibited the strongest interaction with GtfB, whereas myricetin showed the highest affinity toward SpaP. Multiple hydrogen bonds, hydrophobic interactions, and π-mediated contacts contributed to complex stabilization. SwissADME analysis revealed high gastrointestinal absorption and acceptable drug-likeness profiles, particularly for quercetin and kaempferol. Conclusion: Clitoria ternatea flavonoids demonstrated promising anti-cariogenic potential by targeting glucan synthesis and bacterial adhesion pathways of S. mutans. These findings support their further investigation as plant-derived anti-virulence agents for caries prevention and management.