Evidence map›Paper›PMID 22532686›Full record

ArticleJournal of virology2012

Isoflavone agonists of IRF-3 dependent signaling have antiviral activity against RNA viruses.

Kristin M Bedard, Myra L Wang, Sean C Proll, Yueh-Ming Loo, Michael G Katze, Michael Gale, Shawn P Iadonato

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019
    Review
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Kristin M BedardKineta, Inc., Seattle, Washington, USA. kbedard@kineta.us
Myra L Wang
Sean C Proll
Yueh-Ming Loo
Michael G Katze
Michael Gale
Shawn P Iadonato
University of Washington · USKineta (United States) · US

Funding

Agonists of the RIG-I Innate Immune PathwayR44AI081335 · NIAID · KINETA, INC. · PI GALE, MICHAEL, IADONATO, SHAWN PATRICK · 2011 to 2013
$2.7M
Agonists of the RIG-I Innate Immune PathwayR43AI081335 · NIAID · KINETA, INC. · PI IADONATO, SHAWN PATRICK · 2008 to 2009
$585k
NIAID NIH HHS R43 AI081335NIAID NIH HHS R43AI081335NIAID NIH HHS R44 AI081335PHS HHS HSSN 272200900035C
6 · The paper itself

Abstract

There is a growing need for novel antiviral therapies that are broad spectrum, effective, and not subject to resistance due to viral mutations. Using high-throughput screening methods, including computational docking studies and an interferon-stimulated gene 54 (ISG54)-luciferase reporter assay, we identified a class of isoflavone compounds that act as specific agonists of innate immune signaling pathways and cause activation of the interferon regulatory factor (IRF-3) transcription factor. The isoflavone compounds activated the ISG54 promoter, mediated nuclear translocation of IRF-3, and displayed highly potent activity against hepatitis C virus (HCV) and influenza virus. Additionally, these agonists efficiently activated IRF-3 in the presence of the HCV protease NS3-4A, which is known to blunt the host immune response. Furthermore, genomic studies showed that discrete innate immune pathways centered on IRF signaling were regulated following agonist treatment without causing global changes in host gene expression. Following treatment, the expression of only 64 cellular genes was significantly induced. This report provides the first evidence that innate immune pathways dependent on IRF-3 can be successfully targeted by small-molecule drugs for the development of novel broad-spectrum antiviral compounds.

Indexed as

Antiviral AgentsHepacivirusHumansImmunity, InnateImmunologic FactorsInterferon Regulatory Factor-3IsoflavonesOrthomyxoviridaeProtein TransportSignal TransductionVirus ReplicationAntiviral AgentsImmunologic FactorsInterferon Regulatory Factor-3IRF3 protein, humanIsoflavones

Identifiers

PMID22532686
PMCPMC3416323
OpenAlexW2166624496

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.