AUTHOR=Rudraraju Reshma S. , Daher Samer S. , Gallardo-Macias Ricardo , Wang Xin , Neiditch Matthew B. , Freundlich Joel S. 

TITLE=Mycobacterium tuberculosis KasA as a drug target: Structure-based inhibitor design

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1008213

DOI=10.3389/fcimb.2022.1008213

ISSN=2235-2988

ABSTRACT=<p>Recent studies have reported the β-ketoacyl-acyl carrier protein KasA as a druggable target for <italic>Mycobacterium tuberculosis</italic>. This review summarizes the current status of major classes of KasA inhibitors with an emphasis on significant contributions from structure-based design methods leveraging X-ray crystal structures of KasA alone and in complex with inhibitors. The issues addressed within each inhibitor class are discussed while detailing the characterized interactions with KasA and structure-activity relationships. A critical analysis of these findings should lay the foundation for new KasA inhibitors to study the basic biology of <italic>M. tuberculosis</italic> and to form the basis of new antitubercular molecules of clinical significance with activity against drug-sensitive and drug-resistant infections.</p>