4.7 Article

Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets

Journal

SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/srep17759

Keywords

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Funding

  1. National Health and Medical Research Council (NHMRC) of Australia
  2. Australian Research Council (ARC)
  3. Victorian Life Sciences Computation Initiative (VLSCI) grant [VR0007]
  4. Australian Academy of Science
  5. Australian-American Fulbright Commission
  6. Alexander von Humboldt Foundation
  7. Melbourne Water Corporation
  8. Melbourne International Research Scholarships (MIRS)
  9. Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne
  10. Victorian Government

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The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people. Treating this disease by targeted or mass administration with a single chemical, praziquantel, carries the risk that drug resistance will develop in this pathogen. Therefore, there is an imperative to search for new drug targets in S. haematobium and other schistosomes. In this regard, protein kinases have potential, given their essential roles in biological processes and as targets for drugs already approved by the US Food and Drug Administration (FDA) for use in humans. In this context, we defined here the kinome of S. haematobium using a refined bioinformatic pipeline. We classified, curated and annotated predicted kinases, and assessed the developmental transcription profiles of kinase genes. Then, we prioritised a panel of kinases as potential drug targets and inferred chemicals that bind to them using an integrated bioinformatic pipeline. Most kinases of S. haematobium are very similar to those of its congener, S. mansoni, offering the prospect of designing chemicals that kill both species. Overall, this study provides a global insight into the kinome of S. haematobium and should assist the repurposing or discovery of drugs against schistosomiasis.

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