Computational Screening of Plant-Derived Antimicrobial Compounds Against Alpha-Hemolysin of Staphylococcus aureus

The emergence of antibiotic-resistant Staphylococcus aureus poses a critical threat to global public health, necessitating the urgent exploration of alternative antimicrobial strategies. In the present study, we conducted a comprehensive in silico investigation targeting alpha-hemolysin, a key virulence-associated protein of S. aureus , to identify potent plant-derived antimicrobial compounds as prospective alternatives to conventional antibiotics. A total of 19 phytocompounds of diverse botanical origin and 14 commercially used antibiotics spanning multiple generations were evaluated through molecular docking and stability analyses. Among the phytochemicals screened, Procyanidin (PubChem CID: 107876) exhibited the highest binding affinity toward alpha-hemolysin, achieving an average docking score of −7.54 kcal/mol, which was closely comparable to that of the best-performing antibiotic, Virginiamycin M1 + Streptogramin A (PubChem CID: 5459319), with an average docking score of −7.6 kcal/mol. Notably, subsequent Molecular Dynamics Simulation performed using Desmond 2021-2 in the Maestro suite (Schrödinger LLC, New York, NY, USA) revealed that the protein-procyanidin complex demonstrated greater structural stability over time relative to the protein-antibiotic complex. Multiple curated online databases and established computational tools were employed throughout the workflow to ensure the robustness and reliability of the analysis. Collectively, these findings suggest that procyanidin holds considerable promise as a candidate antibacterial agent, warranting further validation through experimental and clinical investigations.