Abstract
Multidrug resistance in M. tb has become a huge global problem due to drug resistance. Hence, the treatment remains a challenge, even though short term chemotherapy is available. Therefore, it is of interest to identify novel drug targets in M.tb through gene expression profiling complimented by a subtractive proteome model. WhiB6 is a transcriptional regulator protein and a known drug resistant marker that is critical in the secretion dependent regulation of ESX-1, which is specialized for the deployment of host membrane-targeting proteins. The WhiB6 protein structure was modelled ab initio and was docked with a library of 173 phytochemicals with potential antituberculosis activity to the identified drug marker to find novel lead molecules. UDP-galactopyranose and GDP-L-galactose were identified to be potential lead molecules to inhibit the target WhiB6. The results were compared with the first line drugs for MDR-TB by docking with WhiB6. Data showed that Ethambutol showed better binding ability to WhiB6 but the afore mentioned top ranked phytochemicals were found to be better candidate molecules. The chosen candidate lead molecules should be further validated by suitable in vitro or in vivo investigation.
Highlights
Every year about 10 million people are affected by tuberculosis and among which 1.6 million people die. [1,2] Across the world about 10 million people developed tuberculosis as of 2017 about two third of all new cases occurred in 8 countries like India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa which are designated the status of high TB burden countries along with 22 other countries
[1] Multidrug resistance in Mycobacterium tuberculosis has emerged as a major problem in treatment even though short-term chemotherapy is available; development of resistance to antibiotics has become a global menace
[5] Exuding antibiotic is due to the impermeable cell wall, that is mediated by efflux mechanisms by several ABC (ATP - binding cassette) transporter and major facilitator super family (MFS) proteins
Summary
Every year about 10 million people are affected by tuberculosis and among which 1.6 million people die. [1,2] Across the world about 10 million people developed tuberculosis as of 2017 about two third of all new cases occurred in 8 countries like India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa which are designated the status of high TB burden countries along with 22 other countries. [1,2] Across the world about 10 million people developed tuberculosis as of 2017 about two third of all new cases occurred in 8 countries like India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa which are designated the status of high TB burden countries along with 22 other countries These countries contribute to 87% of world cases. [6] Currently the growing trends of drug resistance in M.tb have led to a wide range of drug discoveries and to look for the functional protein that which is of key focus to target a lead molecule. In this scenario alternate treatment protocols with lesser toxicity can help clinicians battle MDR TB with greater ease.
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