Network Pharmacology-Based Identification of Key Metabolites from Immunized Rhynchophorus Larvae as Therapeutic Agents Against Antibiotic-Resistant Neisseria gonorrhoea.

<b>Background and Objective:</b> Gonorrhoea, caused by <i>Neisseria gonorrhoeae</i>, continues to pose a major global health threat due to the rising incidence of antibiotic resistance. This study aimed to explore the potential of metabolites derived from immunized larvae of <i>Rhynchophorus</i> sp., as alternative therapeutic agents for the treatment of gonorrhea. <b>Materials and Methods:</b> Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) was used to identify metabolites from the hemolymph of larvae immunized with non-pathogenic <i>Escherichia coli</i>. Subsequently, key molecular targets of these metabolites were identified through network pharmacology and molecular docking approaches. <b>Results:</b> Metabolite interaction networks revealed L-glutamic acid as the compound with the highest degree of interaction (25) among the 15 identified amino acid-derived metabolites. Further analysis of gene interactions identified <i>guaA</i>, which encodes guanosine monophosphate synthetase, as having the highest degree of interaction (27). Binding-free energy of identified metabolites, with L-tryptophan showing the highest binding free energy of -5.9 kcal/mol in the guanosine monophosphate receptor. <b>Conclusion:</b> The study identifies guanosine monophosphate synthetase (GMPS) as a promising target for combating gonorrhea, with L-tryptophan showing potential as a lead compound. Targeting GMPS disrupts critical metabolic pathways in <i>N. gonorrhea</i>, offering a novel approach against antibiotic-resistant strains. By integrating metabolite analysis, network pharmacology and molecular docking, the study provides a comprehensive framework for drug discovery. This multidisciplinary strategy advances the development of effective therapies for antibiotic-resistant pathogens.