Covalent Inhibitors Targeting Mycobacterial Enzymes: Current Status, Challenges and Future Perspectives

This review offers a critical and comprehensive overview of the most promising covalent inhibitors against traditional and emerging enzymatic targets of Mycobacterium tuberculosis (Mtb). Nearly three decades after the World Health Organisation’s (WHO) declaration of tuberculosis (TB) as a global health emergency, Mtb continues to claim millions of lives, remaining among the leading causes of death worldwide. In recent years, several efforts have been devoted to shortening and improving treatment outcomes and to overcoming increasing drug resistance. The aim of our work is to provide a perspective on recent progress in the field of covalent inhibitors of mycobacterial enzymes, highlighting the current landscape and outlining future directions for safer and more effective strategies.