High-throughput screening and molecular dynamics simulations of natural products targeting LuxS/AI-2 system as a novel antibacterial strategy for antibiotic resistance in Helicobacter pylori

The main goal of treating any Helicobacter pylori (H. pylori)-related gastrointestinal disease is completely eradicating infection. Falling eradication efficiency, off-target effects, and patient noncompliance with prolonged and broad spectrums have sparked clinical interest in exploring other effective, safer therapeutic choices. As natural substances are risk-free and privileged with high levels of antibacterial activity, most of these natural chemical's specific modes of action are unknown. With the aid of in silico molecular docking-based virtual screening studies and molecular dynamic simulations, the current study is intended to gather data on numerous such natural chemicals and assess their affinity for the S-ribosyl homocysteine lyase (LuxS) protein of H. pylori. The ligand with the highest binding energy with LuxS, glucoraphanin, catechin gallate and epigallocatechin gallate were rationally selected for further computational analysis. The solution stability of the three compounds' optimal docking postures with LuxS was initially assessed using long-run molecular dynamics simulations. Using molecular dynamics simulation, the epigallocatechin gallate was found to be the most stable molecule with the highest binding free energy, indicating that it might compete with the natural ligand of the inhibitors. According to ADMET analysis, his phytochemical was a promising therapeutic candidate for an antibacterial action since it had a range of physicochemical, pharmacokinetic, and drug-like qualities and had no discernible adverse effects. Additional in vitro, in vivo, and clinical trials are needed to confirm the drug's precise efficacy during H. pylori infection.Communicated by Ramaswamy H. Sarma

Automated summary

The study aims to explore effective and safer therapeutic choices than current methods for treating Helicobacter pylori (H. pylori)-related gastrointestinal disease. Using molecular docking and molecular dynamics simulation, the affinity of numerous natural chemicals for the LuxS protein of H. pylori was evaluated. Glucoraphanin, catechin gallate, and epigallocatechin gallate were found to have the highest binding energy and stable docking postures with LuxS. Epigallocatechin gallate showed the highest binding free energy and promising antibacterial qualities according to ADMET analysis.