A small molecule called C48 starves tuberculosis by cutting off its internal vitamin supply, turning a supposedly impossible drug target into a simple daily pill.
April 25, 2026
Original Paper
Validating Conditionally Essential Targets: Discovery of the First Orally Effective Biotin Inhibitor against MycobacteriumTuberculosis
bioRxiv · 2025.09.24.678246
The Takeaway
Tuberculosis bacteria rely on a specific enzyme called BioA to manufacture the biotin they need to survive inside a human host. Previous attempts to block this enzyme failed because potential drugs could not survive the digestive system or reach the infection site in high enough concentrations. This new compound C48 survives oral delivery and binds to the target enzyme with extreme precision. Testing shows it significantly reduces the bacterial burden in the lungs of living subjects for the first time. This breakthrough provides a new way to fight drug resistant strains that kill over a million people annually. Future treatments could finally replace toxic injections with a straightforward pill that attacks the bacteria from the inside out.
From the abstract
Conditionally essential pathways - such as the biotin biosynthesis - represent promising targets for new antibiotics. However, the chemical interrogation of the biotin pathway with an orally effective lead remains elusive, and the preclinical development of biotin inhibitors for mycobacterial infections in vivo is challenging due to the unusually high concentration of biotin in standard mouse models. Structure-guided optimization was applied to develop the first oral lead targeting aminotransfer