Tuberculosis (TB) is caused due to Mycobacterium tuberculosis and it has become the serious health issue worldwide. This ailment has caused death of millions of people mostly in the developing countries. According to WHO, 95% of the TB cases prevail in developing countries, and among them 25% patients die1.
Experts have suggested that some metabolic pathways can be selected as a drug target because these few pathways are mandatory for the causal organisms to exist. Accordingly, Tricarboxylic acid cycle (TCA) is considered as a major metabolic pathway of M. tuberculosis, as its genome has to encode an entire TCA cycle2.
Isocitrate dehydrogenase is crucial in citric acid cycle and catalyses oxidative decarboxylation. Mycobacterium tuberculosis isocitrate dehydrogenase-II (mtbicd2) is NADP+ dependent enzyme, but it shows dissimilarity with isocitrate dehydrogenase present in humans3. The citric acid cycle is vital for survival of this causal agent. Scientists have introduced the drug namely. mtbicd2, its potential as a molecular drug target has been confirmed4.
Accordingly, research team led by Swapnil Mishra5 conducted a research, in which in silico investigation of 35 natural compounds against suggested drug target (isocitrate dehydrogenase type II (PDBID: 5 KVU) was performed. Moreover, the purpose of this study was to discover a safe medicine having no side effects.
In this experiment, research team collected crystal structure of isocitrate dehydrogenase II from protein data bank (PDB). Moreover, drug affinity of all the natural compounds was also crosschecked and they were obtained from Pubchem database. Afterwards, scientists conducted Docking investigations and used Autodock 4.0. NADP+ as a reference ligand to compare the docking outcomes with natural compounds. Additionally, molecular dynamics of the docked complex were also determined as well.
At the end of this experiment, scientists found that mtbicd2 can serve as a potential drug target few particular natural compounds can inhibit mtbicd2. Furthermore, Molecular docking as well as molecular dynamics simulation revealed the solidity and satisfactory interactions of target enzyme with amentoflavone (a natural beneficial compound) as compared to other tested compounds. Therefore, this specific compound can be used as a useful antituberculosis compound to treat tuberculosis as well as for health recovery. Additionally, it will not have any unfavorable effect on human health and by utilizing this compound; there will be least chances of developing resistant by M. tuberculosis as well.
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17 August, 2019