Identification of potential drug targets and inhibitor of the pathogenic bacteria Shigella flexneri 2a through the subtractive genomic approach

Abstract

Shigella flexneri 2a is one of the most pathogenic bacteria among the Shigella spp., which is responsible for dysentery and causes masses of deaths throughout the world per year. A proper identification of the potential drug targets and inhibitors is crucial for the treatment of the shigellosis due to their emerging multidrug resistance (MDR) patterns. In this study, a systematic subtractive approach was implemented for the identification of novel therapeutic targets of S. flexneri 2a (301) through genome-wide metabolic pathway analysis of the essential genes and proteins. Ligand-based virtual screening and ADMET analyses were also made for the identification of potential inhibitors as well. Initially, we found 70 essential unique proteins as novel targets. After subsequent prioritization, finally we got six unique targets as the potential therapeutic targets and their three-dimensional models were built thereafter. Aspartate-β-semialdehyde dehydrogenase (ASD), was the most potent target among them and used for docking analysis through ligand-based virtual screening. The compound 3 (PubChem CID: 11319750) suited well as the best inhibitor of the ASD through ADMET and enzyme inhibition capacity analysis. To end, we hope that our proposed therapeutic targets and its inhibitors might give some breakthrough to treat shigellosis efficiently in in vitro.

Pharmacoinformatics based elucidation and designing of potential inhibitors against Plasmodium falciparum to target importin α/β mediated nuclear importation

“…These would lead us to design small molecule inhibitors targeting this active site to inhibit the formation of heterodimer α/β. Application of energy minimization through GROMOS 96 force field steps also prepares the model ready to dock organization on its large active site pocket (Oany et al 2018).…”

Design of novel viral attachment inhibitors of the spike glycoprotein (S) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through virtual screening and dynamics

“…The scientific communities are working hard to develop some therapeutics such as vaccines or drugs [ 19 , [60] , [61] , [62] , [63] ]. Computational biology approaches are becoming very much promising for treating many severe diseases through projecting the in vitro validations [64] , [65] , [66] , [67] , [68] .…”

Identification of molecular pathways and prognostic biomarkers with survival analysis associated with UV-mediated skin cancer by bioinformatics approaches

“…The advancement of bioinformatics techniques, next-generation sequencing, proteomics, transcriptomics, and epigenetic research has enhanced our understanding of cancer growth and molecular processes and the design of appropriate drugs for the diseases. Recently, a promising technology called integrated system biology has been used to identify new molecular oncogenes and gene signatures utilizing Gene Expression Omnibus (GEO) gene expression profiles already in existence [32,49,40,41]. Most existing bioinformatics studies focus on oncogene changes and neglect differences at the protein level, and molecular biology validation is seldom performed.…”