ArticlePLoS neglected tropical diseases2017
CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM).
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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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
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Fatal brain infection in early life: primary amoebic meningoencephalitis caused by Naegleria fowleri in neonates and infants.BMC infectious diseases · 2026Pooled it
- Promising Drug Repurposing Candidates Targeting Free-Living Amoebae: A Systematic and Critical Review of Laboratory-Based Evidence.Pathogens (Basel, Switzerland) · 2026Pooled it
- Transgenic approaches in the pathogenic free-living amoebae: what are the hurdles?Parasitology · 2026Review
- Article
- The Activity of FDA-Approved Prodrug Isavuconazonium Sulfate and Its Major Metabolite Isavuconazole AgainstPharmaceutics · 2026Article
- A review of the mechanism, diagnosis, and treatment ofFrontiers in microbiology · 2025Review
- Control Phytophagous Nematodes By Engineering Phytosterol Dealkylation Caenorhabditis elegans as a Model.Molecular biotechnology · 2024Article
- Approaches for TargetingPathogens (Basel, Switzerland) · 2024Review
- Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads.Biomolecules · 2024Review
- Utilizing metagenomic next-generation sequencing and phylogenetic analysis to identify a rare pediatric case ofFrontiers in microbiology · 2024Article
- Miconazole-like Scaffold is a Promising Lead forJournal of medicinal chemistry · 2023Article
- The anti-amoebic potential of carboxamide derivatives containing sulfonyl or sulfamoyl moieties against brain-eating Naegleria fowleri.Parasitology research · 2023Article
- Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.Frontiers in microbiology · 2023Article
- Virtual Screening of Alkaloid and Terpenoid Inhibitors of SMT Expressed inMolecules (Basel, Switzerland) · 2022Article
- An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism inMicroorganisms · 2022Article
- Differential Growth Rates andMicrobiology spectrum · 2022Article
- Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease.Frontiers of medicine · 2021Review
- The transcriptome of Balamuthia mandrillaris trophozoites for structure-guided drug design.Scientific reports · 2021Article
- Primary Amoebic Meningoencephalitis byBiomolecules · 2021Review
- Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads.Expert review of anti-infective therapy · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered "rare" (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug 'repurposing'-a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially 'druggable' target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.