Tuberculosis (TB) is a leading infectious disease caused by Mycobacterium tuberculosiswith high morbidity and mortality. Isocitrate lyase (MtbICL), a key enzyme of glyoxylate pathway has been shown to be involved in the persistence, is attractive drug target against persistent mycobacteria. Virtual screening, molecular docking and MD simulation study has been integrated for screening of phytochemical based anti-mycobacterial compounds. Docking study of reported MtbICL inhibitors has shown an average binding affinity score -7.30 Kcal/mol.In virtual screening, Compounds exhibiting lower binding energy than calculated average binding energy were selected as top hit compounds followed by calculation of drug likeness property.Relationship between experimental IC50 value and calculated binding gibbs free energy of reported inhibitors was calculated trough regression analysis to predict IC50 value of potential inhibitors. Docking and MD simulation studies of top hit compounds have identified shinjudilactone (quassinoid), lecheronol A (pimarane) and caniojane (diterpene) as potential MtbICL inhibitors.
Keywords: Isocitrate lyase, Mycobacterial persistence, Molecular docking, MD simulation, Tuberculosis and Virtual screening.
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