Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets

Abstract

Neisseria gonorrhoeae is an emerging multidrug resistance pathogen that causes sexually transmitted infections in men and women. The N. gonorrhoeae has demonstrated an emerging antimicrobial resistance against reported antibiotics, hence fetching the attention of researchers to address this problem. The present in-silico study aimed to find putative novel drug and vaccine targets against N. gonorrhoeae infection by the application of bioinformatics approaches. Core genes set of 69 N. gonorrhoeae strains was acquired from complete genome sequences. The essential and non-homologous metabolic pathway proteins of N. gonorrhoeae were identified. Moreover, different bioinformatics databases were used for the downstream analysis. The DrugBank database scanning identified 12 novel drug targets in the prioritized list. They were preferred as drug targets against this bacterium. A viable vaccine is unavailable so far against N. gonorrhoeae infection. In the current study, two outer-membrane proteins were prioritized as vaccine candidates via reverse vaccinology approach. The top lead B and T-cells overlapped epitopes were utilized to generate a chimeric vaccine construct combined with immune-modulating adjuvants, linkers, and PADRE sequences. The top ranked prioritized vaccine construct (V7) showed stable molecular interaction with human immune cell receptors as inferred during the molecular docking and MD simulation analyses. Considerable response for immune cells was interpreted by in-silico immune studies. Additional tentative validation is required to ensure the effectiveness of the prioritized vaccine construct against N. gonorrhoeae infection. The identified proteins can be used for further rational drug and vaccine designing to develop potential therapeutic entities against the multi-drug resistant N. gonorrhoeae.

Deciphering the Immunogenicity of Monkeypox Proteins for Designing the Potential mRNA Vaccine

“…The epitopes were filtered based on a rank of <2.0 or lower for MHC–II binding epitopes. The projected epitope’s capacity to engage with MHC molecules increases with decreasing rank. , …”

“…The projected epitope's capacity to engage with MHC molecules increases with decreasing rank. 31,32 2.3. T-Cell-Predicted Epitope Analysis.…”

Structural informatics approach for designing an epitope-based vaccine against the brain-eating Naegleria fowleri

“…Furthermore, their physicochemical properties were checked using the Protparam Expasy server ( 22 ) and the TMHMM server was used to check the topology values of all proteins. The most antigenic, stable, and non-allergenic proteins were selected as the vaccine candidates ( 23 , 24 ).…”

“…The V1-Receptor complexes were subjected to Molecular Dynamic Simulations for determining the complex stability. The TLR2 & TLR4 as receptors and the vaccine V1 as ligand were prepared as per the standard protocol of GROMACS as performed in our recent study ( 23 ). The constructed complexes were subjected to production run of 100 ns and results were analyzed using vmd and in house scripts.…”

An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine

“…Subcellular location of protein is important for identifying appropriate vaccine targets [44]. To predict subcellular localizations of the proteins PSORTb version3.0 was used (https://www.psort.org/psortb/) [45].…”