Novel Bumped Kinase Inhibitors Are Safe and Effective Therapeutics in the Calf Clinical Model for Cryptosporidiosis.

Autor:	Schaefer DA; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson., Betzer DP; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson., Smith KD; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson., Millman ZG; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson., Michalski HC; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson., Menchaca SE; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson., Zambriski JA; Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman., Ojo KK; Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease., Hulverson MA; Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease., Arnold SL; Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease., Rivas KL; Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease., Vidadala RS; Department of Chemistry., Huang W; Department of Biochemistry, University of Washington, Seattle., Barrett LK; Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease., Maly DJ; Department of Chemistry.; Department of Biochemistry, University of Washington, Seattle., Fan E; Department of Biochemistry, University of Washington, Seattle., Van Voorhis WC; Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease., Riggs MW; School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2016 Dec 15; Vol. 214 (12), pp. 1856-1864. Date of Electronic Publication: 2016 Oct 17.
DOI:	10.1093/infdis/jiw488
Abstrakt:	Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a diarrheal disease that has produced a large global burden in mortality and morbidity in humans and livestock. There are currently no consistently effective parasite-specific pharmaceuticals available for this disease. Bumped kinase inhibitors (BKIs) specific for parasite calcium-dependent protein kinases (CDPKs) have been shown to reduce infection in several parasites having medical and veterinary importance, including Toxoplasma gondii, Plasmodium falciparum, and C. parvum In the present study, BKIs were screened for efficacy against C. parvum infection in the neonatal mouse model. Three BKIs were then selected for safety and clinical efficacy evaluation in the calf model for cryptosporidiosis. Significant BKI treatment effects were observed for virtually all clinical and parasitological scoring parameters, including diarrhea severity, oocyst shedding, and overall health. These results provide proof of concept for BKIs as therapeutic drug leads in an animal model for human cryptosporidiosis. (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
Databáze:	MEDLINE
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