title: Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets.
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.
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Stroehlein
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Young
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Jex
authors.affiliation: HHMI, Division of Biology, California Institute of Technology, Pasadena, California, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.affiliation: Genome Institute of Singapore, Republic of Singapore.|Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Republic of Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Boag
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.|Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Robin B
authors.initials: RB
authors.lastname: Gasser
mesh_terms: D000818:Animals; D019295:Computational Biology; D016503:Drug Delivery Systems; D055808:Drug Discovery; D006801:Humans; D010770:Phosphotransferases / Q000096:biosynthesis / Q000235:genetics*; D012548:Schistosoma haematobium / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D012553:Schistosomiasis haematobia / Q000188:drug therapy* / Q000469:parasitology; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D010770:Phosphotransferases