ArticlePLoS neglected tropical diseases2018
Screening of the Pathogen Box for inhibitors with dual efficacy against Giardia lamblia and Cryptosporidium parvum.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed.
- Article
- Pentamidine inhibition of streptopain attenuatesMicrobiology spectrum · 2025Article
- Pentamidine inhibition of streptopain attenuatesbioRxiv : the preprint server for biology · 2025Article
- Preparation, Characterization, and Oral Bioavailability of Solid Dispersions ofInternational journal of molecular sciences · 2024Article
- Medicines for Malaria Venture Pandemic Box In Vitro Screening Identifies Compounds Highly Active against the Tachyzoite Stage ofTropical medicine and infectious disease · 2023Article
- Tyrosine Kinase Inhibitors Display Potent Activity against Cryptosporidium parvum.Microbiology spectrum · 2023Article
- Preliminary Structure-Activity Relationship Study of the MMV Pathogen Box Compound MMV675968 (2,4-Diaminoquinazoline) Unveils Novel Inhibitors ofMolecules (Basel, Switzerland) · 2022Article
- Antibiofilm agents with therapeutic potential against enteroaggregative Escherichia coli.PLoS neglected tropical diseases · 2022Article
- Repurposing the Kinase Inhibitor Mavelertinib for Giardiasis Therapy.Antimicrobial agents and chemotherapy · 2022Article
- Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Synthesized Magnolol Derivatives Improve Anti-Viruses · 2022Article
- Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.Frontiers in cellular and infection microbiology · 2022Review
- In vitro growth inhibitory activity of Medicines for Malaria Venture pathogen box compounds against Leishmania aethiopica.BMC pharmacology & toxicology · 2021Article
- Article
- Pyrrolopyrimidine Bumped Kinase Inhibitors for the Treatment of Cryptosporidiosis.ACS infectious diseases · 2021Article
- Recent advances in genetic manipulation of Cryptosporidium.Current opinion in microbiology · 2020Review
- An Antiparasitic Compound from the Medicines for Malaria Venture Pathogen Box PromotesACS infectious diseases · 2020Article
- Methionyl-tRNA synthetase inhibitor has potent in vivo activity in a novel Giardia lamblia luciferase murine infection model.The Journal of antimicrobial chemotherapy · 2020Article
- Whole-Cell Phenotypic Screening of Medicines for Malaria Venture Pathogen Box Identifies Specific Inhibitors ofAntimicrobial agents and chemotherapy · 2020Article
- An image-based Pathogen Box screen identifies new compounds with anti-Giardia activity and highlights the importance of assay choice in phenotypic drug discovery.International journal for parasitology. Drugs and drug resistance · 2020Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
There is need for a more efficient cell-based assay amenable to high-throughput drug screening against Giardia lamblia. Here, we report the development of a screening method utilizing G. lamblia engineered to express red-shifted firefly luciferase. Parasite growth and replication were quantified using D-luciferin as a substrate in a bioluminescent read-out plateform. This assay was validated for reproducibility and reliability against the Medicines for Malaria Venture (MMV) Pathogen Box compounds. For G. lamblia, forty-three compounds showed ≥ 75% inhibition of parasite growth in the initial screen (16 μM), with fifteen showing ≥ 95% inhibition. The Pathogen Box was also screened against Nanoluciferase expressing (Nluc) C. parvum, yielding 85 compounds with ≥ 75% parasite growth inhibition at 10 μM, with six showing ≥ 95% inhibition. A representative set of seven compounds with activity against both parasites were further analyzed to determine the effective concentration that causes 50% growth inhibition (EC50) and cytotoxicity against mammalian HepG2 cells. Four of the seven compounds were previously known to be effective in treating either Giardia or Cryptosporidium. The remaining three shared no obvious chemical similarity with any previously characterized anti-parasite diarrheal drugs and offer new medicinal chemistry opportunities for therapeutic development. These results suggest that the bioluminescent assays are suitable for large-scale screening of chemical libraries against both C. parvum and G. lamblia.
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