Molecular Docking Analysis of Selected Natural Compounds, Targeting Streptococcus pyogenes and Streptococcus agalactiae, and Preliminary Clinical Pilot Evaluation of a Local Vaginal Formulation: Implications for Localized Antimicrobial Strategies

Streptococcus pyogenes and Streptococcus agalactiae are major Gram-positive patho-gens implicated in recurrent and invasive genital infections, and the rise of antimicrobial resistance underscores the need for alternative localized therapies. This study combined molecular docking with a prospective pilot clinical evaluation of an essential-oil-based vaginal capsule formulation intended for localized intravaginal administration. Terpinen-4-ol, isoflavone, and secoisolariciresinol diglucoside (SDG) were analyzed against two bacterial targets - the redox-sensing transcriptional repressor Rex from S. agalactiae and the protein tyrosine phosphatase from S. pyogenes - using the 1-Click Docking platform and the Lamarckian Genetic Algorithm. In parallel, 47 women aged 19-27 years were identified with vaginal and/or cervical colonization or infection caused by S. agalactiae or S. pyogenes, and 34 of them entered a prospective pilot treatment study with once-daily vaginal capsules for 7 days; persistent positive cases received an additional 7-day course. Isoflavone and SDG showed the most favorable interactions against the S. agalactiae target, while SDG also displayed comparatively favorable interaction against the S. pyogenes target. In the clinical pilot cohort, microbiological eradication after completion of therapy reached 91.7% for S. agalactiae and 80.0% for S. pyogenes. The parallel trend between stronger in silico prioritization for the S. agalactiae-directed target and higher clinical eradication in the pilot cohort supports a cautious translational hypothesis, but the absence of a control group, the limited sample size, and the exploratory nature of the clinical dataset require restrained interpretation. Overall, these findings support further controlled studies designed to test whether the computationally prioritized phytocompounds contribute to measurable in vivo benefit within localized antimicrobial strategies.