Table 6 List of TB host targets or compounds proposed in this study

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.