AUTHOR=Oh Sangmi , Trifonov Lena , Yadav Veena D. , Barry Clifton E. , Boshoff Helena I. 

TITLE=Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.611304

DOI=10.3389/fcimb.2021.611304

ISSN=2235-2988

ABSTRACT=<p>More than two decades have elapsed since the publication of the first genome sequence of <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to clinical testing. Whole-cell screening followed by elucidation of mechanism of action has to date been the most fruitful approach to progressing inhibitors into the tuberculosis drug discovery pipeline although target-based approaches are gaining momentum. This review discusses scaffolds that have been identified over the last decade from screens of small molecule libraries against <italic>Mtb</italic> or defined targets where mechanism of action investigation has defined target-hit couples and structure-activity relationship studies have described the pharmacophore.</p>