Aim and Objective: One of the challenges to conventional therapies against
Mycobacterium tuberculosis is the development of multi-drug resistant pathogenic strains. This
study was undertaken to explore new therapeutic targets for the revolutionary antivirulence therapy
utilizing the pathogen’s essential hypothetical proteins, serving as virulence factors, which is the
essential first step in novel drug designing.
Methods: Functional annotations of essential hypothetical proteins from Mycobacterium
tuberculosis (H37Rv strain) were performed through domain annotation, Gene Ontology analysis,
physicochemical characterization and prediction of subcellular localization. Virulence factors
among the essential hypothetical proteins were predicted, among which pathogen-specific drug
target candidates, non-homologous to human and gut microbiota, were identified. This was
followed by druggability and spectrum analysis of the identified targets.
Results and Conclusion: The study successfully assigned functions of 83 essential hypothetical
proteins of Mycobacterium tuberculosis, among which 25 were identified as virulence factors. Out
of 25, 12 virulence factors were observed as potential pathogen-specific drug target candidates.
Nine potential targets had druggable properties and rest three were considered as novel targets.
Exploration of these targets will provide new insights into future drug development.
Characterization of subcellular localizations revealed that most of the predicted targets were
cytoplasmic which could be ideal for intracellular drugs, while two drug targets were membranebound,
ideal for vaccines. Spectrum analysis identified one broad-spectrum and 11 narrowspectrum
targets. This study would, therefore, instigate designing novel therapeutics for
antivirulence therapy, which have the potential to serve as revolutionary treatment instead of
conventional antibiotic therapies to overcome the lethality of antibiotic-resistant strains.