Virtual screening for inhibitors of shikimate kinase of Mycobacterium tuberculosis

Objective: The objective of the present work is to select a target in an essential metabolic pathway of Mycobacterium tuberculosis and identify the target specific inhibitor in the small molecular database to improve treatment of multi-drug resistant tuberculosis (MDR_TB). In the present work shikimate kinase is selected as target to develop novel drug against Mycobacterium tuberculosis.Methods: Shikimate kinase (SK) and other enzymes in the shikimate pathway are potential targets for developing new anti-tuberculosis drugs, because this pathway is essential to bacteria but absent in mammals. Ligands in ZINC database are screened for the active site binding of this enzyme using i-dock and Arguslab.Results: Screening of ZINC database taking molecular mass in 300-500 range and other physico-chemical properties suitable for drug-like molecules, yields 12855 numbers of ligands. Docking of these molecules to the active site of SK gives a list of hits in the descending order of binding energies. Best 10 out of 1000 hits are considered to select leads. These best ten hits are analysed through Molsoft online tool for drug-likeness and ProTox tool for oral toxicity. The best two from the list of hits passing the drug-likeness and toxicity test are considered as the lead molecules for the development of anti-tubercular drug.Conclusions: Structure based virtual screening and examination of drug-likeness, toxicity and other molecular properties, suggest two molecules as leads. They require further validation studies.