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Reverse vaccinology and subtractive genomics approaches for identifying common therapeutics against Mycobacterium leprae and Mycobacterium lepromatosis

Arun Kumar Jaiswal1,2, Sandeep Tiwari1, Syed Babar Jamal3, Letícia de Castro Oliveira1,2, Helioswilton Sales-Campos2,4, Leonardo Eurípedes Andrade-Silva6, Carlo Jose Freire Oliveira2, Preetam Ghosh5, Debmalya Barh7, Vasco Azevedo1, Siomar C. Soares2, Virmondes Rodrigues Junior2, Marcos Vinicius da Silva2 [ + show more ]

J Venom Anim Toxins incl Trop Dis, 2021, 27:e20200027
Received: 04 March 2020 | Accepted: 09 December 2020 | Published online: 09 April 2021
https://doi.org/10.1590/1678-9199-JVATITD-2020-0027

Abstract

Background: Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world. The elimination of leprosy cannot be achieved by multidrug therapy alone, and highlights the need for new tools and drugs to prevent the emergence of new resistant strains. Methods: In this study, our contribution includes the prediction of vaccine targets and new putative drugs against leprosy, using reverse vaccinology and subtractive genomics. Six strains of Mycobacterium leprae and Mycobacterium lepromatosis (4 and 2 strains, respectively) were used for comparison taking Mycobacterium leprae strain TN as the reference genome. Briefly, we used a combined reverse vaccinology and subtractive genomics approach. Results: As a result, we identified 12 common putative antigenic proteins as vaccine targets and three common drug targets against Mycobacterium leprae and Mycobacterium lepromatosis. Furthermore, the docking analysis using 28 natural compounds with three drug targets was done. Conclusions: The bis-naphthoquinone compound Diospyrin (CID 308140) obtained from indigenous plant Diospyros spp. showed the most favored binding affinity against predicted drug targets, which can be a candidate therapeutic target in the future against leprosy.

 

Keywords: Mycobacterium lepraeMycobacterium lepromatosis; Leprosy; Vaccine targets; Drug target identification.

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