Emerging Targets in Anti-Tubercular Drug Design

Keith D. Green, Selina Y.L. Holbrook, Huy X. Ngo, Sylvie Garneau-Tsodikova

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Scopus citations

Abstract

Tuberculosis (TB) is currently the second most lethal infection following HIV. In 2014 alone, there were 9.6 million new cases of TB and 1.5 million TB-related deaths reported worldwide. It is also estimated that about one third of the entire population carries latent Mycobacterium tuberculosis (Mtb), the etiological cause of TB. These individuals are asymptomatic, but can develop a full TB infection if left untreated. The current first-line TB treatment consists of a cocktail of isoniazid, rifampicin, pyrazinamide, and ethambutol. A fraction of Mtb strains develop resistance to isoniazid and rifampicin and are usually treated with second-line anti-tubercular agents, such as aminoglycosides, fluoroquinolones, or the antimicrobial peptide capreomycin. Some strains acquire further resistance to second-line treatments, causing a significantly higher mortality rate. The increase of drug-resistant Mtb strains has triggered action in the scientific field, which has led to a renaissance in anti-tubercular drug discovery with multiple emerging drug targets. Herein, we summarize the latest enzymes, pathways, and mechanisms presented in the literature (covering 2000-2016) related to the emergence of promising targets in anti-tubercular drug design.

Original languageEnglish
Title of host publicationAllosterism in Drug Discovery
EditorsDavid Thurston, Troy Lister, Steven M. Firestine
Pages141-203
Number of pages63
Edition58
DOIs
StatePublished - 2017

Publication series

NameRSC Drug Discovery Series
Number58
Volume2017-January
ISSN (Print)2041-3203
ISSN (Electronic)2041-3211

Bibliographical note

Funding Information:
The author is grateful to Gwenola Auda-Boucher and Yvonnick Cheraud for their collaboration during this research, Martine Molina for typing the manuscript, Felix Crossin for contributing photographic materials, Thierry Rouaud and Maryvonne Zampieri for their technical assistance, and Dr. James Gray for reading the manuscript. This work was supported by the University of Nantes, the Centre National de la Recherche Scientifique, and the Association Franeaise contre les Myopathies.

Publisher Copyright:
© The Royal Society of Chemistry 2017.

ASJC Scopus subject areas

  • Drug Discovery

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