Molecular docking of a set of flavonoid compounds with Helicobacter pylori virulence factors CagA and VacA

Introduction: Cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (VacA) proteins are the main Helicobacter pylori virulence factors. These toxins are associated with severe gastric diseases. Flavonoids are plant secondary metabolites that have shown great antibacterial effects. This work aimed to study the interaction of a set of flavonoid compounds with CagA and VacA proteins using molecular docking. Methods: A set of 54 flavonoid compounds were used in this study, and 36 of which passed the Lipinski rules of 5. The 3D structures of CagA and VacA proteins were obtained from the Protein Data Bank. The molecular docking was performed using AutoDock Vina software and the results were expressed in terms of binding energies (kcal/mol). Protein-ligand interactions were analyzed using PyMOL software. Results: For the CagA protein, the licochalcone A molecule showed the highest binding affinity (-8 kcal/mol). For the VacA protein, the galangin, luteolin, and apigenin molecules showed the highest binding affinity (-8.9, -8.5, and -8.2 kcal/mol, respectively). Interactions of the licochalcone A, galangin, luteolin, and apigenin with CagA and VacA proteins involved their hydroxyl groups and/or their carbonyl groups. Conclusion: Our study showed that these compounds might have the potential for their development into drugs for controlling H. pylori pathogenicity.