Computational Exploration of Flavonoids in Drug Delivery Frameworks for Targeting Staphylococcus aureus Virulence

Abstract

The increasing prevalence of multidrug-resistant Staphylococcus aureus poses a significant global health concern, driving the search for safer and more effective therapeutic alternatives. Flavonoids, a diverse class of plant-derived polyphenolic compounds, exhibit potent antimicrobial, antioxidant, and anti-inflammatory activities, making them promising candidates for the development of targeted drug delivery systems. Incorporating flavonoids into delivery platforms such as liposomes, polymeric nanoparticles, or hydrogels can enhance their solubility, stability, and site-specific release while maintaining bioavailability and minimising systemic side effects. Such systems enable the controlled and localised delivery of bioactive molecules to the infection site, thereby enhancing therapeutic efficacy. In this study, we propose a drug delivery-based approach utilising flavonoids to counteract S. aureus pathogenesis, with a particular focus on toxin inhibition. Computational techniques were employed to predict the binding affinity and stability of flavonoid interactions with key virulence factors such as Staphylococcal Enterotoxin A. The docking and simulation analyses revealed strong and stable binding conformations, suggesting that specific flavonoids could interfere with toxin activity and reduce bacterial virulence. These findings highlight the dual potential of flavonoids as both natural inhibitors and bioactive components in advanced drug delivery systems. This integrated strategy offers valuable insights into the rational design of novel, flavonoid-based antimicrobial therapeutics aimed at mitigating S. aureus infections.