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Because of the apparent stasis in antibiotic discoveries and the growth of multidrug resistance, Helicobacter pylori-associated gastric infections are difficult to eradicate. In the search for alternative therapy, the reductive amination of chitosan with mannose, followed by ionic gelation, produced mannose functionalized chitosan nanoparticles. Then, molecular docking and molecular dynamics (MD) simulations were conducted with H. pylori lectin (HPLectin) as a target protein involved in bacterium adherence to host cells, biofilm formation, and cytotoxicity. Changes in zeta potential and FTIR spectroscopy revealed that chitosan was functionalized with mannose. Time-kill, polystyrene adherence, and antibiofilm studies were utilized to assess nanoparticles as an alternative antibacterial treatment against a resistant gastric pathogen. Man-CS-Nps were discovered to have effective anti-adherence and biofilm disruption …