Targeting the multidrug efflux pump; Tap protein to reduce survival of Mycobacterium tuberculosis

<title>Abstract</title> <italic>Tuberculosis</italic> (TB) is a serious communicative disease caused by a bacterium named <italic>Mycobacterium</italic> <italic>tuberculosis</italic>. Albeit there are vaccines and drugs available to treat the disease, Multidrug-resistant TB (MDR-TB) is still one of the most critical challenges for the investigators where the development of efflux systems makes them resistant to drugs. Tap is a multidrug efflux pump and proposed to have a significant role in the survival of <italic>M. tuberculosis </italic>making it drug-resistant. In the present study, we have utilized various <italic>In silico</italic> approaches to predict the applicability of FDA approved ion channel inhibitors and blockers as therapeutic leads against Tuberculosis. We have analysed 18 inhibitor compounds and eventually screened three ligands as drugs, Glibenclimide, Lubiprostone and Flecainde that have displayed the novel stable binding with Tap protein aiming to affect or inhibit its activity. Structure of Tap protein is predicted by Phyre2 server followed by its characterization by 10ns MD simulations using the CABS-flex 2.0 server and validation by Ramachandran plot. PyRx software presented the binding affinity varied in the range of -8.00 kcal/mol to -9.8 kcal/mol, implies that the drug molecules can spontaneously interact with the target protein. Amongst them, Glibenclimide shows the highest binding affinity with ΔG of -9.8 kcal/mol. This study proposed Tap protein as an interesting drug target and investigated drugs may show considerable effects on the target protein showing a novel therapeutic lead against Tuberculosis.