Unveiling DprE1 as a Key Target in the Fight against Tuberculosis: Insights and Perspectives on Developing Novel Antimicrobial Agents

Abstract

Amid the global health crisis instigated by COVID-19, the resurgence of tuberculosis (TB) has underscored the urgent need for innovative solutions. With TB claiming 1.6 million lives in 2021, it remains a formidable challenge, particularly in underdeveloped regions. Central to Mycobacterium tuberculosis (Mtb) pathogenesis is the decaprenylphosphoryl-β-D-ribose oxidase (DprE1)/decaprenylphosphoryl-2-keto-β-D-erythropentose reductase (DprE2) complex, pivotal for synthesizing decaprenylphosphoryl-arabinofuranose (DPA), a critical component of mycobacterial cell walls. DprE1 has emerged as a prime therapeutic target, with several inhibitors in clinical trials. This review elucidates the indispensability of DprE1, examines existing ligands, and delineates key considerations for the development of next-generation anti-TB therapeutics. Our analysis highlights the potential of DprE1 inhibitors to revolutionize TB treatment, emphasizing the need for continued research and development in this area to address the evolving landscape of TB and drug resistance.