Examples of current therapies under investigation | Targets and compounds proposed in this study | ||||
---|---|---|---|---|---|
Compounds | Targets/Pathways | Evidence [45] | Compounds | Targets/Pathways | Evidence |
Aspirin | Arachidonic acid metabolism | Upregulation of lipoxin X4 production to reduce TNF-α levels and achieve eicosanoid balance during chronic inflammation. | LRRK2 inhibitor | LRRK2 pathway | LRRK2 pathway significantly upregulated in TB. LRRK2 genetically associated with susceptibility of M. leprae infection. Cormobidities between TB and Parkinson’s disease. |
Anti-CTLA4/PD-1/TIM3/LAG3 | Modulation of aberrant T-cell activity | Blockade of immune checkpoint pathways to restore T- and B-cell activity. | PD-L1 inhibitor (Atezolizumab) | PD-1/PD-L1 pathway | PD-1/PD-L1 significantly upregulated in TB, and inhibit TB-specific T-cell and macrophage functions. |
Valproic acid | Histone acetylation | Removal of acetyl groups of lysine residues on histones to allow DNA unwinding and gene transcription. | Carfizomib | PSMB8, PSMB9, PSMB10, PSMB2 | PSMB8, PSMB9 significantly upregulated in TB, with strong genetic association with TB infection. |
Statins | Disruption of cholesterol homeostasis | Abrogates production of endogenous cholesterol. | Intraveneous Immunoglobulin (IVIg) | FCGR2A, FCGR3A, C5 | FCGR2A, FCGR3A, C5 significantly upregulated in TB. Efficacy of IVIg in reducing bacterial load in TB infection. |
Verapamil/Carbamazepine | Modulation of ion efflux channels | Modulation of activity of voltage-gated channels to maintain cellular ionic balance and homeostasis. | Disopyramide | SCN5A, ORM1 | Top compound in CMAP analysis. SCN5A regulates spatial and temporal calcium signaling during Mtb phagocytosis. |
Metformin | Mitochondrial respiration | Interrupts the mitochondrial respiratory chain and induces ROS production. | Flunarizine | HRH1, CACNA1G, CACNA1H, CACNA1I, CALM1 | Top compound in CMAP analysis. Potential efficacy in restricting Mtb growth. |