Treating cryptosporidiosis: A review on drug discovery strategies.

Int J Parasitol Drugs Drug Resist

University of Lille, CNRS, Centrale Lille, Junia, Université Polytechnique Hauts de France, UMR 8520, IEMN Institut d'Electronique de Microélectronique et de Nanotechnologie, F, 59000, Lille, France. Electronic address:

Published: August 2024

Despite several decades of research on therapeutics, cryptosporidiosis remains a major concern for human and animal health. Even though this field of research to assess antiparasitic drug activity is highly active and competitive, only one molecule is authorized to be used in humans. However, this molecule was not efficacious in immunocompromised people and the lack of animal therapeutics remains a cause of concern. Indeed, the therapeutic arsenal needs to be developed for both humans and animals. Our work aims to clarify research strategies that historically were diffuse and poorly directed. This paper reviews in vitro and in vivo methodologies to assess the activity of future therapeutic compounds by screening drug libraries or through drug repurposing. It focuses on High Throughput Screening methodologies (HTS) and discusses the lack of knowledge of target mechanisms. In addition, an overview of several specific metabolic pathways and enzymatic activities used as targets against Cryptosporidium is provided. These metabolic processes include glycolytic pathways, fatty acid production, kinase activities, tRNA elaboration, nucleotide synthesis, gene expression and mRNA maturation. As a conclusion, we highlight emerging future strategies for screening natural compounds and assessing drug resistance issues.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11066572PMC
http://dx.doi.org/10.1016/j.ijpddr.2024.100542DOI Listing

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