ArticleAntimicrobial agents and chemotherapy2013
A cysteine protease inhibitor rescues mice from a lethal Cryptosporidium parvum infection.
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 37 papers.
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Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
- Mouse Models for Use in Cryptosporidium Infection Studies, Quantification of Parasite Burden Using Flow Cytometry, qPCR and Histopathology, and Confocal Imaging of Oocysts.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Norditerpene Natural Products from Subterranean Fungi with Anti-Parasitic Activity.Microorganisms · 2025Article
- Cryptosporidium parvum multidrug resistance protein confers resistance to toxic gut microbial metabolite.Cell host & microbe · 2025Article
- Molecular pathogenesis of Cryptosporidium and advancements in therapeutic interventions.Parasite (Paris, France) · 2025Review
- Sequence introgression from exogenous lineages underlies genomic and biological differences among Cryptosporidium parvum IOWA lines.Water research · 2024Article
- A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments.Antibodies (Basel, Switzerland) · 2024Review
- Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.Life (Basel, Switzerland) · 2024Review
- Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens-Factors Linked to Virulence and Pathogenicity.International journal of molecular sciences · 2023Review
- Enrichment and proteomic identification of Cryptosporidium parvum oocyst wall.Parasites & vectors · 2022Article
- An update onJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Review
- High infectivity and unique genomic sequence characteristics of Cryptosporidium parvum in China.PLoS neglected tropical diseases · 2022Article
- The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.Frontiers in cellular and infection microbiology · 2022Review
- An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives.Frontiers in cellular and infection microbiology · 2022Review
- Severe acute respiratory syndrome-coronavirus-2: Current advances in therapeutic targets and drug development.Reviews in medical virology · 2021Review
- Purification and Characterization of a Novel Thermostable Papain Inhibitor fromPharmaceutics · 2021Article
- Article
- A cysteine protease inhibitor blocks SARS-CoV-2 infection of human and monkey cells.bioRxiv : the preprint server for biology · 2020Article
- Recent discovery and development of inhibitors targeting coronaviruses.Drug discovery today · 2020Review
- Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis.Nature communications · 2019Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium parvum, can stunt infant growth and can be lethal in immunocompromised individuals. The most widely used drugs for treating cryptosporidiosis are nitazoxanide and paromomycin, although both exhibit limited efficacy. To investigate an alternative approach to therapy, we demonstrate that the clan CA cysteine protease inhibitor N-methyl piperazine-Phe-homoPhe-vinylsulfone phenyl (K11777) inhibits C. parvum growth in mammalian cell lines in a concentration-dependent manner. Further, using the C57BL/6 gamma interferon receptor knockout (IFN-γR-KO) mouse model, which is highly susceptible to C. parvum, oral or intraperitoneal treatment with K11777 for 10 days rescued mice from otherwise lethal infections. Histologic examination of untreated mice showed intestinal inflammation, villous blunting, and abundant intracellular parasite stages. In contrast, K11777-treated mice (210 mg/kg of body weight/day) showed only minimal inflammation and no epithelial changes. Three putative protease targets (termed cryptopains 1 to 3, or CpaCATL-1, -2, and -3) were identified in the C. parvum genome, but only two are transcribed in infected mammals. A homology model predicted that K11777 would bind to cryptopain 1. Recombinant enzymatically active cryptopain 1 was successfully targeted by K11777 in a competition assay with a labeled active-site-directed probe. K11777 exhibited no toxicity in vitro and in vivo, and surviving animals remained free of parasites 3 weeks after treatment. The discovery that a cysteine protease inhibitor provides potent anticryptosporidial activity in an animal model of infection encourages the investigation and development of this biocide class as a new, and urgently needed, chemotherapy for cryptosporidiosis.
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