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dc.contributor.authorNawaratna, Sujeevi SK
dc.contributor.authorMcManus, Donald P
dc.contributor.authorGasser, Robin B
dc.contributor.authorBrindley, Paul J
dc.contributor.authorBoyle, Glen M
dc.contributor.authorRivera, Vanessa
dc.contributor.authorRanasinghe, Shiwanthi L
dc.contributor.authorJones, Malcolm K
dc.contributor.authorYou, Hong
dc.contributor.authorGobert, Geoffrey N
dc.date.accessioned2020-08-19T00:33:24Z
dc.date.available2020-08-19T00:33:24Z
dc.date.issued2020
dc.identifier.issn1469-8161
dc.identifier.doi10.1017/S0031182020001250
dc.identifier.urihttp://hdl.handle.net/10072/396533
dc.description.abstractPraziquantel (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 inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47-68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherCambridge University Press (CUP)
dc.relation.ispartofjournalParasitology
dc.subject.fieldofresearchVeterinary sciences
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchcode3009
dc.subject.fieldofresearchcode3207
dc.subject.keywords1Naphthyl PP1
dc.subject.keywordsCaMK
dc.subject.keywordsCaMKII
dc.subject.keywordsSTSP
dc.subject.keywordsSchistosoma mansoni
dc.titleUse of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationNawaratna, SSK; McManus, DP; Gasser, RB; Brindley, PJ; Boyle, GM; Rivera, V; Ranasinghe, SL; Jones, MK; You, H; Gobert, GN, Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy., Parasitology, 2020
dc.date.updated2020-08-18T03:20:44Z
dc.description.versionAccepted Manuscript (AM)
gro.description.notepublicThis publication has been entered in Griffith Research Online as an advanced online version.
gro.rights.copyright© 2020 Cambridge University Press. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorNawaratna, Sujeevi S.
gro.griffith.authorBoyle, Glen M.


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