{
  "abstract": "While RNA is an emerging therapeutic target class, progress is limited by a shortage of well-defined targets in which ligand binding is coupled to measurable function. The group I intron, a self-splicing ribozyme essential in fungal mitochondria but absent from humans, offers both a tractable platform for exploring first principles of small molecule-RNA targeting and a selective antifungal target. We recalibrated an intron-splicing assay to approximate cellular conditions and performed an extensive, cryo-EM-guided structure-activity relationship campaign against the Candida albicans mtLSU intron. Ligands containing a flexible diamine outperformed conformationally constrained analogues, suggesting a general principle for engaging dynamic RNA surfaces and yielding lead aminopyridine 56 (IC 21.6 nM). Compound 56 synergizes with amphotericin B against C. albicans, suggesting a path for combination therapies. RT-qPCR confirmed direct target engagement in cells. This work establishes the fungal group I intron as a viable, mechanistically distinct antifungal target and a model platform for RNA-targeted discovery.",
  "abstract_shown": true,
  "affiliations": [
    "Yale University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "J. Hwang"
    },
    {
      "name": "L. J. Sisto"
    },
    {
      "name": "T. Shi"
    },
    {
      "name": "M. C. Van Zandt"
    },
    {
      "affs": [
        0
      ],
      "name": "A. M. Pyle"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f67cpnmd2pnh8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.764270",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764270v1.full",
  "id": "f67cpnmd2pnh8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764270v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biochemistry"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764270v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f67cpnmd2pnh8.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:02Z",
      "native_id": "10.64898/2026.11.04.764270",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764270v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biochemistry",
      "subfield": "general"
    }
  ],
  "title": "RNA-targeted aminopyridine compounds provide a new antifungal strategy",
  "title_text": "RNA-targeted aminopyridine compounds provide a new antifungal strategy",
  "type": "preprint",
  "updated_at": "2026-11-08T00:20:58Z",
  "url": "https://research.draconitic.com/paper/f67cpnmd2pnh8",
  "venue": "bioRxiv",
  "versions": []
}