ArticlePLoS neglected tropical diseases2020
Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae.
Article in PLoS neglected tropical diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 64 citations in OpenAlex.
- New Viability Assays for Acanthamoeba castellanii Trophozoites and Cysts Allow Rapid Assessment of Drug Activity.The Journal of infectious diseases · 2026Article
- Transgenic approaches in the pathogenic free-living amoebae: what are the hurdles?Parasitology · 2026Review
- Development of Approaches for Transgene Expression in the Pathogenic Free-Living AmoebaPathogens (Basel, Switzerland) · 2025Article
- The potential of nanocomposites (patuletin-conjugated with gallic acid-coated zinc oxide) against free-living amoebae pathogens.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Secreted small RNAs ofbioRxiv : the preprint server for biology · 2025Article
- Phosphonium chloride-based deep eutectic solvents inhibit pathogenic Acanthamoeba castellanii belonging to the T4 genotype.Folia microbiologica · 2025Article
- Computational discovery of potential therapeutic agents against brain-eating amoeba (Naegleria fowleri).PloS one · 2025Article
- Research Progress in Mutagenesis Techniques forMini reviews in medicinal chemistry · 2025Review
- Case Report: Management of Acanthamoeba Rhinosinusitis in a Patient with Chronic Lymphocytic Leukemia.The American journal of tropical medicine and hygiene · 2024Article
- Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation.Archives of microbiology · 2024Article
- Novel anti-Frontiers in cellular and infection microbiology · 2024Article
- Emerging patents versus brain eating amoebae,Pharmaceutical patent analyst · 2024Review
- Utilizing metagenomic next-generation sequencing and phylogenetic analysis to identify a rare pediatric case ofFrontiers in microbiology · 2024Article
- Glucose metabolism in the pathogenic free-living amoebae: Tempting targets for treatment development.Chemical biology & drug design · 2024Review
- Nanocarrier Drug Conjugates Exhibit Potent Anti-Diseases (Basel, Switzerland) · 2023Article
- Anti-Balamuthia mandrillaris and anti-Naegleria fowleri effects of drugs conjugated with various nanostructures.Archives of microbiology · 2023Article
- Pathogenic free-living amoebic encephalitis from 48 cases in China: A systematic review.Frontiers in neurology · 2023Review
- Encephalomyelomeningitis Caused byInfection and drug resistance · 2023Article
- Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.Frontiers in microbiology · 2023Article
- Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report.Open life sciences · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diseases caused by pathogenic free-living amoebae include primary amoebic meningoencephalitis (Naegleria fowleri), granulomatous amoebic encephalitis (Acanthamoeba spp.), Acanthamoeba keratitis, and Balamuthia amoebic encephalitis (Balamuthia mandrillaris). Each of these are difficult to treat and have high morbidity and mortality rates due to lack of effective therapeutics. Since repurposing drugs is an ideal strategy for orphan diseases, we conducted a high throughput phenotypic screen of 12,000 compounds from the Calibr ReFRAME library. We discovered a total of 58 potent inhibitors (IC50 <1 μM) against N. fowleri (n = 19), A. castellanii (n = 12), and B. mandrillaris (n = 27) plus an additional 90 micromolar inhibitors. Of these, 113 inhibitors have never been reported to have activity against Naegleria, Acanthamoeba or Balamuthia. Rapid onset of action is important for new anti-amoeba drugs and we identified 19 compounds that inhibit N. fowleri in vitro within 24 hours (halofuginone, NVP-HSP990, fumagillin, bardoxolone, belaronib, and BPH-942, solithromycin, nitracrine, quisinostat, pabinostat, pracinostat, dacinostat, fimepinostat, sanguinarium, radicicol, acriflavine, REP3132, BC-3205 and PF-4287881). These compounds inhibit N. fowleri in vitro faster than any of the drugs currently used for chemotherapy. The results of these studies demonstrate the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. Given that many of the repurposed drugs have known mechanisms of action, these compounds can be used to validate new targets for structure-based drug design.
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