ArticleAntimicrobial agents and chemotherapy2013
Drug repurposing screen reveals FDA-approved inhibitors of human HMG-CoA reductase and isoprenoid synthesis that block Cryptosporidium parvum growth.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 135 citations in OpenAlex.
- Structure-Activity Relationship Study of Anti-Cryptosporidium Benzoxaboroles Yields Enhanced Potency and Curative Efficacy.Journal of medicinal chemistry · 2026Article
- Genomic heterogeneity of NAD(P)H dehydrogenase predisposes Cryptosporidium to clofazimine resistance.Nature microbiology · 2026Article
- High-Content Screening for Cryptosporidium Drug Discovery.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Phenotypic High-Throughput Screening and Drug Efficacy Test Against the Growth of Cryptosporidium parvum In Vitro by qRT-PCR.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Pathogenicity and virulence ofVirulence · 2025Review
- Article
- Widespread genomic heterogeneity at the type II NAD(P)H dehydrogenase locus predisposesbioRxiv : the preprint server for biology · 2025Article
- Synthesis of β-fluoropyrrolidines designed to reduce hERG affinity in a class of antiparasitic compounds.ChemistrySelect · 2025Article
- Discovery of an Orally Efficacious Pyrazolo[3,4-Journal of medicinal chemistry · 2025Article
- Exploration of innovative drug repurposing strategies for combating human protozoan diseases: Advances, challenges, and opportunities.Journal of pharmaceutical analysis · 2025Review
- Article
- Identification of potent and orally efficacious phosphodiesterase inhibitors in Cryptosporidium parvum-infected immunocompromised male mice.Nature communications · 2024Article
- Molecular Targets of the 5-Amido-Carboxamide Bumped Kinase Inhibitor BKI-1748 inInternational journal of molecular sciences · 2024Article
- Evaluation of the therapeutic efficacy of some essential oils in experimentally immunosuppressed mice infected withJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2023Article
- Specific pathway abundances in the neonatal calf faecal microbiome are associated with susceptibility to Cryptosporidium parvum infection: a metagenomic analysis.Animal microbiome · 2023Article
- Structure-Activity Relationship Studies of the Aryl Acetamide Triazolopyridazines againstJournal of medicinal chemistry · 2023Article
- Investigation of the prophylactic and therapeutic effectiveness of oral thyme extract in rats experimentally infected with cryptosporidium parvum.Veterinary research communications · 2023Article
- Structure-Activity relationships of replacements for the triazolopyridazine of Anti-Cryptosporidium lead SLU-2633.Bioorganic & medicinal chemistry · 2023Article
- Tyrosine Kinase Inhibitors Display Potent Activity against Cryptosporidium parvum.Microbiology spectrum · 2023Article
- The Marine Compound Tartrolon E Targets the Asexual and Early Sexual Stages ofMicroorganisms · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cryptosporidiosis, a diarrheal disease usually caused by Cryptosporidium parvum or Cryptosporidium hominis in humans, can result in fulminant diarrhea and death in AIDS patients and chronic infection and stunting in children. Nitazoxanide, the current standard of care, has limited efficacy in children and is no more effective than placebo in patients with advanced AIDS. Unfortunately, the lack of financial incentives and the technical difficulties associated with working with Cryptosporidium parasites have crippled efforts to develop effective treatments. In order to address these obstacles, we developed and validated (Z' score = 0.21 to 0.47) a cell-based high-throughput assay and screened a library of drug repurposing candidates (the NIH Clinical Collections), with the hopes of identifying safe, FDA-approved drugs to treat cryptosporidiosis. Our screen yielded 21 compounds with confirmed activity against C. parvum growth at concentrations of <10 μM, many of which had well-defined mechanisms of action, making them useful tools to study basic biology in addition to being potential therapeutics. Additional work, including structure-activity relationship studies, identified the human 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor itavastatin as a potent inhibitor of C. parvum growth (50% inhibitory concentration [IC(50)] = 0.62 μM). Bioinformatic analysis of the Cryptosporidium genomes indicated that the parasites lack all known enzymes required for the synthesis of isoprenoid precursors. Additionally, itavastatin-induced growth inhibition of C. parvum was partially reversed by the addition of exogenous isopentenyl pyrophosphate, suggesting that itavastatin reduces Cryptosporidium growth via on-target inhibition of host HMG-CoA reductase and that the parasite is dependent on the host cell for synthesis of isoprenoid precursors.
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Registered trials
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