{
  "abstract": "Retinoic acid-inducible gene-I (RIG-I) plays a pivotal role in recognizing and combating RNA viruses in humans, and it has become a drug target of significant interest. RIG-I agonists composed of dsRNA represent antiviral and antitumor therapies, however the development of small-molecule RIG-I agonists, with their potential for improved pharmacokinetics, remains an unmet need. Here, we report small-molecule RIG-I agonists that directly activate the RIG-I receptor protein. These agonists stimulate the first step in RIG-I signaling by triggering release of the signaling domains (CARDs) from an autorepressed form of the protein. This was achieved by developing a sensitive high-throughput screening (HTS) assay that directly monitors CARD expulsion through optical methods. The resulting screen hits were refined and optimized, leading to a specific RIG-I agonist that induces a robust interferon response. This study establishes a pharmacophore and assay for development of small molecules that precisely modulate RIG-I signaling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Rong Guo"
    },
    {
      "name": "Kenneisha Norford"
    },
    {
      "name": "Ling Xu",
      "orcid": "0000-0002-9057-0829"
    },
    {
      "name": "Manyi Wei"
    },
    {
      "name": "Wenshuai Wang",
      "orcid": "0000-0002-8713-9923"
    },
    {
      "name": "Stephanie Halene",
      "orcid": "0000-0002-2737-9810"
    },
    {
      "name": "Anna Marie Pyle",
      "orcid": "0000-0001-9045-8872"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2r45jaeb63taf.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77982-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13680500",
  "id": "2r45jaeb63taf",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-77982-3",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7222956891",
  "pdf_url": "https://www.nature.com/articles/s41467-026-77982-3.pdf",
  "pmcid": "PMC13680500",
  "pmid": "42897194",
  "published": "2026-10-19",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/2r45jaeb63taf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "10.1038/s41467-026-77982-3",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-77982-3"
    },
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42897194",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897194"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "Discovery of direct-acting small-molecule RIG-I agonists through creation of a selective CARD activation platform",
  "title_text": "Discovery of direct-acting small-molecule RIG-I agonists through creation of a selective CARD activation platform",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/2r45jaeb63taf",
  "venue": "Nature Communications",
  "versions": []
}