Introduction Neisseria gonorrhoeae is an etiologic agent of one of the most common sexually transmitted disease in humans. The continuous rise of N. gonorrhoeae infection worldwide accompanied by rapid emergence of multidrug-resistant and hypervirulent strains has necessitated the search for novel drug targets and their inhibitors. The present study is undertaken to screen inhibitors against the novel drug targets of N. gonorrhoea.
Methods The putative therapeutic targets in N. gonorrhoeae were identified by in silico approach which encompassed similarity search between pathogen and host, essentiality study using the database of essential genes and metabolic functional association study using Kyoto Encyclopaedia of Genes and Genomes database. Virtual screening of inhibitors against the major candidate therapeutic targets was further carried out using docking analysis. In vitro protein inhibitor binding assays are proposed for the best docked compounds.
Results The study identified various promising drug targets which are non-homologous to human proteins, essential for the pathogen and present in important pathogen-specific pathways. The peptidoglycan biosynthesis pathway is the highest donor to the list of candidate target proteins followed by the two component system. Homology model of one of the identified potential targets from both these pathways, namely, glutamate racemase (product of murI gene) from peptidoglycan biosynthesis pathway and NarL protein from two component system, was constructed. Subsequently, by means of virtual screening approach, potential inhibitors from small molecules databases were predicted against both these targets. Identified inhibitors possesed better docking scores and stronger binding affinity with the target molecules compared to known inhibitors and natural substrate of these proteins. These novel compounds may facilitate the development of new drugs to combat increasing drug resistance associated with N. gonorrhoeae.
Conclusion Potential inhibitors predicted against N. gonorrhoeae in the present study opens new avenues for the treatment option against multidrug resistant strains.
Disclosure of interest statement There is no conflict of interest.
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