Targeting Fibronectin-Binding Proteins in Staphylococcus aureus: In Silico Discovery and Pharmacokinetic Profiling of Novel Anti-Adhesion Inhibitors

Staphylococcus aureus is a highly virulent Gram-positive bacterium of global concern due to its potent virulence factors and antimicrobial resistance, causing severe morbidity and mortality. This study employed an anti-virulence approach that targets Fibronectin-binding proteins (FnBPs), key adhesion and immune-evasion determinants, offering an alternative to traditional antibiotics. Computational screening identified inhibitors, including Benzoic Acid (−8.61 kcal/mol), ML346 (−7.34 kcal/mol), and Gallic Acid (−7.29 kcal/mol), which showed strong binding potential. ADMET profiling confirmed good pharmacokinetic behavior and compliance with Lipinski’s Rule of Five. These results highlight small-molecule inhibitors of FnBPs that can disrupt a major virulence pathway in S. aureus, providing a computational foundation for anti-virulence therapy development requiring experimental validation.