Targeting protein kinases for the development of novel drugs for trematode infections

Protein kinases regulate a plethora of vital cellular processes such as metabolism, cell cycle and differentiation and are compelling targets for drug discovery. Inhibition of trematode-specific protein kinases is therefore a potentially viable approach for the discovery new drugs for trematode infections. Several kinase inhibitors have been shown to be microfilaricidal illustrating the potential of repurposing kinase inhibitors for trematode infections. We have elucidated the kinomes of C. sinensis, F. hepatica, O. viverrini and combined this data with published kinomes of S. haematobium, S. japonicum and S. mansoni to decipher several trematode-specific protein kinases that are putative drug targets. These include ERK7, NIM1, DYRK1, GSK, STKR, SYK and the previously identified PAKA and PKA. Computational docking of select kinase inhibitors onto candidate kinase targets is a potentially viable high throughput technique that can be used to identify the most promising kinase inhibitors for further evaluation