Bumped kinase inhibitor 1369 is effective against Cystoisospora suis in vivo and in vitro

Publication date: Available online 2 April 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Aruna Shrestha, Kayode K. Ojo, Florian Koston, Bärbel Ruttkowski, Rama S.R. Vidadala, Carlie S. Dorr, Edelmar D. Navaluna, Grant R. Whitman, Kayleigh F. Barrett, Lynn K. Barrett, Matthew A. Hulverson, Ryan Choi, Samantha A. Michaels, Dustin J. Maly, Andrew Hemphill, Wesley C. Van Voorhis, Anja JoachimAbstractCystoisosporosis is a leading diarrheal disease in suckling piglets. With the confirmation of resistance against the only available drug toltrazuril, there is a substantial need for novel therapeutics to combat the infection and its negative effects on animal health. In closely related apicomplexan species, bumped kinase inhibitors (BKIs) targeting calcium-dependent protein kinase 1 (CDPK1) were shown to be effective in inhibiting host-cell invasion and parasite growth. Therefore, the gene coding for Cystoisospora suis CDPK1 (CsCDPK1) was identified and cloned to investigate activity and thermal stabilization of the recombinant CsCDPK1 enzyme by BKI 1369. In this comprehensive study, the efficacy, safety and pharmacokinetics of BKI 1369 in piglets experimentally infected with Cystoisospora suis (toltrazuril-sensitive, Wien-I and toltrazuril-resistant, Holland-I strains) were determined in vivo and in vitro using an established animal infection model and cell culture, respectively. BKI 1369 inhibited merozoite proliferation in intestinal porci...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research