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

Abstract

Introduction: Cytotoxin associated gene A (CagA) and Vacuolating cytotoxin (VacA) proteins are the main Helicobacter pylori (H. 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.

Re-Emergence of Circulation of Seasonal Influenza during COVID-19 Pandemic in Russia and Receptor Specificity of New and Dominant Clade 3C.2a1b.2a.2 A(H3N2) Viruses in 2021–2022

“…The molecular docking method was used to further analyze the receptor binding properties. The molecular docking method is commonly used for the research of ligand-protein interactions, prediction of binding affinities, and binding poses in drug development [63,64]. Autodock Vina [22] is a relatively new program for molecular docking combining Monte Carlo and gradient-based algorithms for the conformation search and a simple scoring function for interaction evaluations.…”

Insights into the Pharmacological Effects of Flavonoids: The Systematic Review of Computer Modeling

“…Flavones (5-hydroxyflavone) and flavonols (quercetin) have a high affinity for the potassium channel Kir6.1, acting on which some cardiovascular diseases can be treated [ 56 ]. Flavones (luteolin, apigenin) can serve as the basis of drugs that control the pathogenicity of Helicobacter pylori due to their ability to bind to one of the main virulence factors of bacteria of this species—vacuolating cytotoxin protein (VacA) [ 76 ]. Flavonols (quercetin), their glycosides (avicularin, hyperoside), and flavanonols (taxifolin) with comparable effects function as arginase inhibitors, which is a potential target for the development of new approaches to the treatment of leishmaniasis [ 77 ].…”

“…Meta-analyses of scoring functions calculated during molecular docking was studied in [ 54 , 56 , 71 , 73 , 76 , 77 , 78 , 79 ]. General information about the average affinities of each flavonoid group to the biological targets is presented in Table 3 and Table 4 for AutoDock and Glide software, respectively.…”

“…The developed methodology was implemented in the articles ( Figure 5 ) and used for the meta-analysis [ 54 , 56 , 71 , 73 , 76 , 77 , 78 , 79 ]. Whilst this study included a total of eight papers, there is very poor information about the processing of protein targets and the assessment of results of molecular docking.…”

Effects of Exosomes Derived From Helicobacter pylori Outer Membrane Vesicle-Infected Hepatocytes on Hepatic Stellate Cell Activation and Liver Fibrosis Induction

“…Genetic arrangement and the presence of virulence factors dramatically determine the outcome of H. pylori infections. Previous studies showed that CagA and VacA factors are the most crucial virulence factors in H. pylori disease progression ( Jouimyi et al., 2020 ; Mubarakali et al., 2021 ); however, recent studies highlighted the importance of novel virulence factors including outer membrane vesicles (OMVs) ( Jarzab et al., 2020 ; Chew et al., 2021 ).…”