Inhibition of lipopolysaccharide layer by plant-derived molecules: A novel approach to combat Helicobacter pylori

The WHO classifies H. pylori as a critical public health issue. H. pylori is a gram-negative bacterium that causes infections in the stomach lining, contributing to conditions such as gastritis, peptic ulcers, and gastric cancer. The emergence of multidrug resistance in H. pylori presents a major obstacle in treatment, resulting in ineffective therapies and prolonged infections. The lipopolysaccharide biosynthesis pathway plays a crucial role in the survival of H. pylori. UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is an essential enzyme, and its crucial role in disease pathogenesis has positioned LpxC as a highly promising druggable target for targeting H. pylori infection. In this study, we utilized structure-based virtual high-throughput screening of phytochemicals to discover potential inhibitors of LpxC. The selection of hits was initially based on their compliance with the Lipinski rule of 5, along with their toxicological, pharmacokinetic properties, and other drug-like attributes. This was followed by 100 ns molecular dynamics simulations in triplicate and MM/PBSA based binding free energy calculations. These findings indicated that Panicutine interacts strongly and enhances the stability of the LpxC structure, suggesting it as potential inhibitor of LpxC. The outcomes point to future studies to enhance their effectiveness as innovative and cost-effective treatments for H. pylori infections.