Aspartate-β-semialdeyhyde dehydrogenase as a potential therapeutic target of Mycobacterium tuberculosis H37Rv: Evidence from in silico elementary mode analysis of biological network model.

Abstract:

:The emergence of multi-drug resistant strains and co-occurrence of tuberculosis with HIV creates a major burden to the human health globally. Failure of primary antibacterial therapy necessitates the identification of new mycobacterial drugs. In this study, a comprehensive analysis involving bottom-up systems biology approach was applied wherein we have identified potential therapeutic targets of Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis therapeutic targets (aspartate-β-semialdeyhde dehydrogenase [ASD], dihydrodipicolinate reductase and diaminopimelate decarboxylase) based on flux and elementary mode analysis using direct mathematical modeling of the relevant metabolic pathways. Molecular docking and simulation studies of the priority target (ie, ASD) revealed the therapeutic potential of the selected natural products (Huperzine A, Rosmarinic acid, and Curcumin) based ASD inhibitors. The study highlights the crucial role of systems biology in conjunction with molecular interaction (docking) for probing novel leads against an increasingly resistant pathogen, M. tuberculousis.

journal_name

J Cell Biochem

authors

Khan S,Somvanshi P,Bhardwaj T,Mandal RK,Dar SA,Wahid M,Jawed A,Lohani M,Khan M,Areeshi MY,Haque S

doi

10.1002/jcb.26458

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

2832-2842

issue

3

eissn

0730-2312

issn

1097-4644

journal_volume

119

pub_type

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