Bumped kinase inhibitor prohibits egression in Babesia bovis

Veterinary Parasitology
Monica J PedroniAudrey O T Lau

Abstract

Babesiosis is a global zoonotic disease acquired by the bite of a Babesia-infected Ixodes tick or through blood transfusion with clinical relevance affecting humans and animals. In this study, we evaluated a series of small molecule compounds that have previously been shown to target specific apicomplexan enzymes in Plasmodium, Toxoplasma and Cryptosporidium. The compounds, bumped kinase inhibitors (BKIs), have strong therapeutic potential targeting apicomplexa-specific calcium dependent protein kinases (CDPKs). We investigated if BKIs also show inhibitory activities against piroplasms such as Babesia. Using a subset of BKIs that have promising inhibitory activities to Plasmodium and Toxoplasma, we determined that their actions ranged from 100% and no inhibition against Babesia bovis blood stages. One specific BKI, RM-1-152, showed complete inhibition against B. bovis within 48h and was the only BKI that showed noticeable phenotypic changes to the parasites. Focusing our study on this BKI, we further demonstrated that RM-1-152 has Babesia-static activity and involves the prohibition of merozoite egress while replication and re-invasion of host cells are unaffected. The distinct, abnormal phenotype induced by RM-1-152 suggests t...Continue Reading

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Citations

May 31, 2016·Expert Opinion on Drug Discovery·Joachim Müller, Andrew Hemphill
Mar 18, 2020·Cell Transplantation·George Ghartey-KwansahXuehong Xu
Dec 8, 2016·The Journal of Infectious Diseases·Deborah A SchaeferMichael W Riggs
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Aug 22, 2021·Scientific Reports·Hassan HakimiShinichiro Kawazu

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