In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis

Khanra, S. , Juin, S. K., Jawed, J. J., Ghosh, S., Dutta, S., Nabi, S. A., Dash, J., Dasgupta, D., Majumdar, S. and Banerjee, R. (2020) In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis. PLOS Neglected Tropical Diseases, 14(8), e0008575. (doi: 10.1371/journal.pntd.0008575) (PMID:32866156) (PMCID:PMC7491717)

Abstract

Background: Treatment failure and resistance to the commonly used drugs remains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/Principal: Leishmania donovani promastigotes were treated with suramin and studies were performed to determine the extent and mode of cell mortality, cell cycle arrest and other in vitro parameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC) and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings: The in vitro studies revealed the potential efficacy of suramin against the Leishmania parasite. This observation was further substantiated in the in vivo murine model, which demonstrated that upon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and also generate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug. Conclusions/Significance: All experiments affirmed the efficacy of suramin against L. donovani infection, which could possibly lead to its inclusion in the repertoire of drugs against VL.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Khanra, Dr Supriya

Creator Roles

Khanra, S.: Conceptualization, Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review and editing

• Authors: Khanra, S., Juin, S. K., Jawed, J. J., Ghosh, S., Dutta, S., Nabi, S. A., Dash, J., Dasgupta, D., Majumdar, S., and Banerjee, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLOS Neglected Tropical Diseases
• Publisher: Public Library of Science
• ISSN: 1935-2727
• ISSN (Online): 1935-2735
• Copyright Holders: Copyright © 2020 Khanra et al.
• First Published: First published in PLOS Neglected Tropical Diseases 14(8):e0008575
• Publisher Policy: Reproduced under a Creative Commons licence