Computational Evaluation of Natural Compounds for Antibacterial and Anti‐Adhesion Effect on Drug‐Resistant Helicobacter pylori: Molecular Docking and Dynamic Simulations

Six key Helicobacter pylori proteins linked to survival, colonization, adhesion, and drug resistance were selected for the in silico study. Molecular docking of 38 natural compounds identified naringin as a promising anti-H. pylori agent with strong binding affinity. Molecular dynamics simulations (RMSD, RMSF, interaction analysis) and ligand property evaluation confirmed the stability. ADMET profiling validated drug-likeness, supporting naringin as a potential anti-H. pylori candidate.

Abstract

Helicobacter pylori infection significantly damages the human stomach mucosa. This bacterium has established high levels of resistance to conventional drugs, necessitating alternative therapies. In this study, we evaluate, via a computational approach, the efficacy of 38 natural compounds as anti-H. pylori agents targeting six key proteins involved in survival, colonization, adhesion and drugs resistance. The result demonstrated that naringin is the better compounds which interact with the six target proteins (all in one time) displaying an XP GScore with urease (−9.78 kcal/mol), chorismate synthase (−10.93 kcal/mol), penicillin-binding protein (−9.82 kcal/mol), HopQ type I (−6.77 kcal/mol), adhesin BabA (−8.68 kcal/mol), and adhesin SabA (−7.75 kcal/mol). RMSD, RMSF, and protein-ligand contact plot analysis, confirmed the stability of naringin-protein complexes during 100 ns MD simulation. Study of additional ligand interaction properties such as rGyr, SASA, intra-HBs, MolSA, and PSA reinforced this stability. ADMET predictions indicated that naringin has poor gastrointestinal absorption and may serve as a substrate for P-glycoprotein. Toxicity prediction also showed that naringin doesn't induce hepatotoxicity, neurotoxicity, cytotoxicity, carcinogenicity, immunotoxicity, mutagenicity, cytotoxicity but have a possible nephrotoxicity and cardiotoxicity. These results favor the use of naringin for the elaboration of an effective alternative therapeutic agents able to counteract adhesion and colonization of drug-resistant H. pylori.

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