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Review
. 2021 Jan;16(1):59-74.
doi: 10.1080/17460441.2020.1812577. Epub 2020 Sep 7.

Phenotypic screening techniques for Cryptosporidium drug discovery

Melissa S Love  1 , Case W McNamara  1
Affiliations
Free article
Review

Phenotypic screening techniques for Cryptosporidium drug discovery

Melissa S Love et al. Expert Opin Drug Discov. 2021 Jan.
Free article

Abstract

Introduction: Two landmark epidemiological studies identified Cryptosporidium spp. as a significant cause of diarrheal disease in pediatric populations in resource-limited countries. Notably, nitazoxanide is the only approved drug for treatment of cryptosporidiosis but shows limited efficacy. As a result, many drug discovery efforts have commenced to find improved treatments. The unique biology of Cryptosporidium presents challenges for traditional drug discovery methods, which has inspired new assay platforms to study parasite biology and drug screening. Areas covered: The authors review historical advancements in phenotypic-based assays and techniques for Cryptosporidium drug discovery, as well as recent advances that will define future drug discovery. The reliance on phenotypic-based screens and repositioning of phenotypic hits from other pathogens has quickly created a robust pipeline of potential cryptosporidiosis therapeutics. The latest advances involve new in vitro culture methods for oocyst generation, continuous culturing capabilities, and more physiologically relevant assays for testing compounds. Expert opinion: Previous phenotypic screening techniques have laid the groundwork for recent cryptosporidiosis drug discovery efforts. The resulting improved methodologies characterize compound activity, identify, and validate drug targets, and prioritize new compounds for drug development. The most recent improvements in phenotypic assays are poised to help advance compounds into clinical development.

Keywords: Cryptosporidium; in vitro culture; Challenges in Cryptosporidium drug discovery; cryptosporidiosis; drug discovery; high-throughput screening; phenotypic assay; phenotypic screening; pipeline.

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