In Silico Screening of Flavonoids Targeting Staphylococcal Enterotoxin A: Binding Insights and Inhibitory Potential

Abstract

Staphylococcal enterotoxin A (SEA), one of the most virulent enterotoxins secreted by Staphylococcus aureus, causes a serious human health problem due to its superantigenic activity and ability to trigger severe food poisoning even at very low doses. Since no effective natural inhibitors of SEA have been identified to date, this study employs integrated computational approaches involving molecular docking, pharmacokinetic profiling, and molecular dynamics simulations to explore flavonoids as potential novel therapeutic candidates. Docking results revealed strong binding interactions of three compounds with the toxin's active sites. Detailed interaction analyses revealed that these flavonoids formed stable hydrogen bonds and hydrophobic interactions with key residues of SEA, suggesting their capacity to interfere with toxin activity. ADMET profiling indicated favourable pharmacokinetic properties and drug-likeness of these compounds. Furthermore, 100-ns MD simulations were conducted to validate the stability and dynamic behaviour of the SEA–flavonoid complexes. Overall, this comprehensive in silico investigation identifies one compound, semilicoisoflavone, as a promising natural inhibitor of SEA. These findings provide the development of flavonoid-based therapeutic agents after future experimental work to mitigate SEA-mediated pathogenicity.