Repurposing Drugs as Host-Directed Therapy in Tuberculosis

Tuberculosis is a chronic infective respiratory disease that has been known to mankind for centuries and is still responsible for higher rates of morbidity and mortality globally. Repurposing drugs as host-directed therapies as an add-on drug to tuberculosis is a promising scope to study as it may have a significant impact in reducing the treatment duration and complications of tuberculosis. Host-directed therapy is a strategy to target the host and its immune mediators responsible for pro and anti-inflammatory pathways, thus modifying them with drugs to achieve increased bacterial clearance and reduced long-term inflammatory-mediated complications of tuberculosis. Various drugs approved for other indications have been studied in preclinical animal and in vitro studies, as well as clinical trials in tuberculosis. These drugs mainly aim to improve mycobacterial clearance and minimize post-TB consequences by suppressing inflammatory mediators. Drugs such as metformin, imatinib, vitamin D, and (Vascular Endothelial Growth Factors) VEGF drugs are studied for their ability to modulate the anti-inflammatory effects, and drugs, such as doxycycline, corticosteroids, and N-acetylcysteine are being studied for their role as proinflammatory modulators. This repurposing drug helps in using these drugs as an adjuvant in tuberculosis, for which the safety is already established through various clinical trials post-marketing surveillance. However, the interaction of these drugs with the standard anti-tubercular drugs and with the disease needs to be studied. In the near future, this host-directed therapy might unlock various management approaches not only in tuberculosis but also in other infective diseases as the action of drugs is on the host.