Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy
Sujeevi SK Nawaratna, Donald P McManus, Robin B Gasser, Paul J Brindley, Glen M Boyle, Vanessa Rivera, Shiwanthi L Ranasinghe, Malcolm K Jones, Hong You, Geoffrey N Gobert
Parasitology | CAMBRIDGE UNIV PRESS | Published : 2020
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inh..View full abstract
This research was funded by the National Health and Medical Research Council (NHMRC) of Australia. DPM is an NHMRC Senior Principal Research Fellow and Senior Scientist at QIMRB.