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

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    Author
    Stroehlein, AJ; Young, ND; Jex, AR; Sternberg, PW; Tan, P; Boag, PR; Hofmann, A; Gasser, RB
    Date
    2015-12-04
    Source Title
    Scientific Reports
    Publisher
    NATURE RESEARCH
    University of Melbourne Author/s
    Gasser, Robin; Jex, Aaron; Stroehlein, Andreas; Young, Neil; HOFMANN, ANDREAS
    Affiliation
    Veterinary Biosciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Stroehlein, A. J., Young, N. D., Jex, A. R., Sternberg, P. W., Tan, P., Boag, P. R., Hofmann, A. & Gasser, R. B. (2015). Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets. SCIENTIFIC REPORTS, 5 (1), https://doi.org/10.1038/srep17759.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258038
    DOI
    10.1038/srep17759
    Abstract
    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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