Vol.:(0123456789) Biochemical Genetics https://doi.org/10.1007/s10528-024-10709-5 1 3 ORIGINAL ARTICLE D‑Glucosamine is a Potential Urease Inhibitor from Middle Eastern Medicinal Plants for Combatting Helicobacter Pylori Infections; a Molecular Docking and Simulation Approach Mohammed Baqur S. Al‑Shuhaib 1  · Hayder O. Hashim 2  · Jafar M. B. Al‑Shuhaib 3 Received: 3 September 2023 / Accepted: 19 January 2024 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024 Abstract Helicobacter pylori stands as a signifcant risk factor for both peptic and stomach ulcers. Their resistance to the highly acidic host environment primarily stems from their capability to produce urease, an enzyme that rapidly converts urea into NH3 and CO2. These byproducts are crucial for the bacterium’s survival under such harsh conditions. Given the pivotal role of medicinal plants in treating various ail- ments with minimal side efects, there is an urgent need for a natural drug that can efectively eliminate H. pylori by inhibiting urease. Hence, the current study aims to identify the most potent urease inhibitor among the natural compounds found in Middle Eastern medicinal plants, taking into consideration factors such as opti- mal afnity, drug-like properties, pharmacokinetic characteristics, and thermody- namic attributes. In total, 5599 ligand conformers from 151 medicinal plants were subjected to docking against the urease’s active site. The top-ranking natural com- pounds, as determined by their high docking scores, were selected for further analy- sis. Among these compounds, D-glucosamine (PubChem code 439,213) exhibited the most interactions with the crucial amino acid residues in the urease’s active site. Furthermore, D-glucosamine demonstrated superior absorption, distribution, metab- olism, excretion, and toxicity properties compared to other top-ranked candidates. Molecular dynamics simulations conducted over 100 nanoseconds revealed stable root mean square deviations and fuctuations of the protein upon complexation with D-glucosamine. Additionally, the radius of gyration and solvent-accessible surface area values for the D-glucosamine-urease complex were notably lower than those observed in other typical urease-inhibitor complexes. In conclusion, this study pro- vides valuable insights into the potential development of D-glucosamine as a novel urease inhibitor. This promising compound holds the potential to serve as an efec- tive drug for combating H. pylori infections in the near future. Extended author information available on the last page of the article