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Development of a novel cytopathic effect-based phenotypic screening assay against Cryptosporidium

Manjunatha, Ujjini Havaldar and Chao, Alexander and Lee, Boon Heng and Wan, Kah Fei and Selva, Jeremy and Zou, Bin and Gedeck, Peter and Beer, David John and Diagana, Thierry Tidiane and Bonamy, Ghislain (2018) Development of a novel cytopathic effect-based phenotypic screening assay against Cryptosporidium. ACS infectious diseases. ISSN 2373-8227

Abstract

Cryptosporidiosis is a diarrheal disease predominantly caused by Cryptosporidium parvum (Cp) and Cryptosporidium hominis (Ch), apicomplexan parasites which infect the intestinal epithelial cells of their human hosts. The only approved drug for cryptosporidiosis is nitazoxanide, which shows limited efficacy in immunocompromised children, the most vulnerable patient population. Thus, new therapeutics and in vitro infection models are urgently needed to address the current unmet medical need. Toward this aim, we have developed novel cytopathic effect (CPE)-based Cp and Ch assays in human colonic tumor (HCT-8) cells and compared them to traditional imaging formats. Further model validation was achieved through screening a collection of FDA-approved drugs and confirming many previously known anti-Cryptosporidium hits as well as identifying a few novel candidates. Collectively, our data reveals this model to be a simple, functional, and homogeneous gain of signal format amenable to high throughput screening, opening new avenues for the discovery of novel anticryptosporidials.

Item Type: Article
Date Deposited: 13 Feb 2018 00:45
Last Modified: 13 Feb 2018 00:45
URI: https://oak.novartis.com/id/eprint/30124

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