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.
Highlights
The blood fluke Schistosoma haematobium causes urogenital schistosomiasis, a neglected tropical disease (NTD) that affects more than 110 million people
Kinases can be subdivided into serine/threonine-phosphorylating kinases (STKs), tyrosine-phosphorylating kinases (TKs) and kinases that phosphorylate either of these residues
We identified nine kinases belonging to the CK1 group, including three members of the Tau tubulin kinase family (TTBK) and one vaccinia-related kinase (VRK)
Summary
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. Recent research efforts to identify new molecular targets for chemotherapeutic intervention have focused on protein kinases[13,14], because they are involved in signalling cascades of essential regulatory and developmental processes[15,16,17], particular kinase groups have relatively conserved structures[18], and because drugs targeting these enzymes in humans have shown particular potential for the treatment of cancers and other diseases[19,20]. This lobe structure forms a catalytic cleft for substrate and ATP binding[15,22,23]
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