Structural Insights into Enterotoxin B Inhibition by Aromadendrin and Afzelechin Through Docking and Molecular Dynamics Analyses

Abstract

Background: Foodborne illnesses caused by Staphylococcus aureus enterotoxins represent a major public health concern due to their exceptional stability to heat, low pH, and proteolytic digestion. Among these, Staphylococcal enterotoxin B (SEB) is one of the most potent bacterial superantigens, capable of inducing massive cytokine release, inflammation, and, in severe cases, multi-organ failure. The remarkable resistance of SEB under common food processing conditions highlights its toxicological importance in food safety and the urgent need for effective inhibitors.

Methods: The interaction and binding affinity between our ligands and SEB were investigated via molecular docking with Autodock 4.2.2. Detailed structural analysis of the free protein and the protein/ligand complex was then achieved through MD simulations implemented in GROMACS 2019.6 using the AMBER99SB force field.

Results: Docking analysis revealed favorable binding interactions, with the aromadendrin/SEB complex displaying the lowest binding energy compared to afzelechin/SEB. Molecular dynamics simulations further demonstrated that aromadendrin induced structural stabilization and compression of SEB, but afzelechin destabilize SEB with producing greater inhibitory effects.

Conclusion: Natural flavonoids can modulate the structural and functional properties of SEB, thereby reducing its toxic potential. Overall, our results provide structural insights into the inhibition of SEB by natural compounds and highlight aromadendrin and afzelechin as promising food-safe inhibitors. This research opens avenues for developing dietary or nutraceutical strategies aimed at controlling staphylococcal enterotoxin-related food poisoning, contributing to food safety and public health protection.