التفاصيل البيبلوغرافية
| العنوان: |
A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis |
| المؤلفون: |
Ujjini H. Manjunatha, Sumiti Vinayak, Jennifer A. Zambriski, Alexander T. Chao, Tracy Sy, Christian G. Noble, Ghislain M. C. Bonamy, Ravinder R. Kondreddi, Bin Zou, Peter Gedeck, Carrie F. B |
| المصدر: |
Nature, Nature. 546(7658):376-380 |
| سنة النشر: |
2017 |
| الوصف: |
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis. |
| نوع الوثيقة: |
redif-article |
| اللغة: |
English |
| DOI: |
10.1038/nature22337 |
| الإتاحة: |
https://ideas.repec.org/a/nat/nature/v546y2017i7658d10.1038_nature22337.html |
| رقم الأكسشن: |
edsrep.a.nat.nature.v546y2017i7658d10.1038.nature22337 |
| قاعدة البيانات: |
RePEc |
