Harnessing Biological Insight to Accelerate Tuberculosis Drug Discovery

Accounts of Chemical Research
Timothy J de WetValerie Mizrahi

Abstract

Tuberculosis (TB) is the leading cause of mortality globally resulting from an infectious disease, killing almost 1.6 million people annually and accounting for approximately 30% of deaths attributed to antimicrobial resistance (AMR). This despite the widespread administration of a neonatal vaccine, and the availability of an effective combination drug therapy against the causative agent, Mycobacterium tuberculosis (Mtb). Instead, TB prevalence worldwide is characterized by high-burden regions in which co-epidemics, such as HIV, and social and economic factors, undermine efforts to control TB. These elements additionally ensure conditions that favor the emergence of drug-resistant Mtb strains, which further threaten prospects for future TB control. To address this challenge, significant resources have been invested in developing a TB drug pipeline, an initiative given impetus by the recent regulatory approval of two new anti-TB drugs. However, both drugs have been reserved for drug-resistant disease, and the seeming inevitability of new resistance plus the recognized need to shorten the duration of chemotherapy demands continual replenishment of the pipeline with high-quality "hits" with novel mechanisms of action. This represe...Continue Reading

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Citations

Oct 20, 2020·Expert Review of Anti-infective Therapy·Juan Alberto Guevara SalazarJosé Guadalupe Trujillo Ferrara

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