生物多様性、生物探査および開発のジャーナル

Tailored-pharmacophore model to enhance virtual screening and drug discovery: A case study on the identification of potential inhibitors against drug-resistant Mycobacterium tuberculosis (3R)-hydroxyacyl- ACP dehydratase

Abstract

Kgothatso E Machaba

Background: Virtual Screening (VS) is powerful tool in discovering molecular inhibitors which are most likely to bind to drug targets of interest. Herein, we introduce a novel VS approach, so-called ??? tailored-pharmacophore???, in order to explore inhibitors that overcome drug resistance. Results/Methodology: The emergence and spread of drug resistance strains of tuberculosis is one of the most critical issues in health care. A tailored-pharmacophore approach was found promising to identify in silico predicted hit with better binding affinities in case of the resistance mutations in MtbHadAB as compared to thiacetazone, a prodrug used in the clinical treatment of TB. Conclusions: This approach can potentially be enforced for the discovery and design of drugs against a wide range of resistance targets.