Authors: Kunal Gharat, Vikas Jha, Divya Nikumb, Joshua Koli, Vrushali Dhamapurkar, Omkar Parulekar, Diksha Poojari, Simeen Rumani, Aparna Sahu, Shivani Kore, Farzha Khan.
Multidrug-resistant bacteria are now widely recognized as a global threat and a substantial public health concern. Antimicrobial resistance (AMR) is known as a more significant threat to humanity. Multidrug-resistant (MDR)/ Extensively Drug-resistant (XDR) Mycobacterium tuberculosis (M. tb) is a prime example of AMR. Furthermore, treating MDR-TB is more challenging since it demands second-line treatments, which have severe side effects. Genomic & proteomic approaches are employed in pharmaceutical research to identify novel drug targets. A subtractive proteomics approach was applied in this study to identify promising therapeutic targets for the MDR strain M. tb CCDC5180. The subtractive proteome approach of the whole proteome of M. tb CCDC5180 showed a list of 14 essential, cytoplasmic, and unique metabolic proteins discovered to be druggable. Among these 14, only eight proteins were involved in the pathogen's virulence. Finally, two proteins, PrrA and KdpE, were identified as potential novel drug targets, and further docking of these proteins with phytochemicals resulted in two promising compounds Cepharanthine and Alianthone against these novel targets.
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