Evidence map›Paper›PMID 23616652›Full record

ArticleJournal of virology2013

The small molecules AZD0530 and dasatinib inhibit dengue virus RNA replication via Fyn kinase.

Melissanne de Wispelaere, Amy J LaCroix, Priscilla L Yang

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

71 citing papers in PubMed, 124 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Host centric drug repurposing for viral diseases.PLoS computational biology · 2025
    Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Advancements in tyrosine kinase-mediated regulation of innate nucleic acid sensing.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024
    Review
  10. Article
  11. Review
  12. Multiple receptor tyrosine kinases regulate dengue infection of hepatocytes.Frontiers in cellular and infection microbiology · 2024
    Article
  13. Article
  14. Review
  15. Preparing for the next viral threat with broad-spectrum antivirals.The Journal of clinical investigation · 2023
    Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

11 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Melissanne de WispelaereDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Amy J LaCroix
Priscilla L Yang
Harvard University · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KASPER, DENNIS L. · 2003 to 2013
$113.7M
U Mass Boston / DFHCC U54 Partnership (1 of 2)U54CA156732 · NCI · DANA-FARBER CANCER INST · PI WENDY Beth LONDON · 2010 to 2026
$25.6M
Training: Molecular & Cellular Bases of Infectious DiseasesT32AI007417 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Arturo Casadevall · 1994 to 2026
$11.9M
VIRUS-HOST INTERACTIONS IN CANCERT32CA009031 · NCI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KIEFF, ELLIOTT D · 1985 to 2009
$2.4M
Validation of Src kinases as Anti-Dengue Viral TargetsR01AI076442 · NIAID · HARVARD MEDICAL SCHOOL · PI YANG, PRISCILLA LI-NING · 2008 to 2012
$2.1M
Development of Cellular Assays of Dengue Virus InfectionR21NS063845 · NINDS · HARVARD MEDICAL SCHOOL · PI YANG, PRISCILLA LI-NING · 2008 to 2008
$169k
NCI NIH HHS CA156732-01NCI NIH HHS T32 CA009031NCI NIH HHS U54 CA156732NIAID NIH HHS AI76442NIAID NIH HHS R01 AI076442NIAID NIH HHS U54 AI057159NINDS NIH HHS R21 NS063845
6 · The paper itself

Abstract

In this study, we characterized the antiviral mechanism of action of AZD0530 and dasatinib, two pharmacological inhibitors of host kinases, that also inhibit dengue virus (DV) infection. Using Northern blot and reporter replicon assays, we demonstrated that both small molecules inhibit the DV2 infectious cycle at the step of steady-state RNA replication. In order to identify the cellular target of AZD0530 and dasatinib mediating this anti-DV2 activity, we examined the effects of RNA interference (RNAi)-mediated depletion of the major kinases known to be inhibited by these small molecules. We determined that Fyn kinase, a target of both AZD0530 and dasatinib, is involved in DV2 RNA replication and is probably a major mediator of the anti-DV activity of these compounds. Furthermore, serial passaging of DV2 in the presence of dasatinib led to the identification of a mutation in the transmembrane domain 3 of the NS4B protein that overcomes the inhibition of RNA replication by AZD0530, dasatinib, and Fyn RNAi. Although we observed that dasatinib also inhibits DV2 particle assembly and/or secretion, this activity does not appear to be mediated by Src-family kinases. Together, our results suggest that AZD0530 and dasatinib inhibit DV at the step of viral RNA replication and demonstrate a critical role for Fyn kinase in this viral process. The antiviral activity of these compounds in vitro makes them useful pharmacological tools to validate Fyn or other host kinases as anti-DV targets in vivo.

Indexed as

Antibodies, MonoclonalBenzodioxolesBlotting, NorthernBlotting, WesternCell SurvivalDasatinibDengue VirusDimethyl SulfoxideDNA PrimersHEK293 CellsHumansMycophenolic AcidPolymerase Chain ReactionProtein Kinase InhibitorsProto-Oncogene Proteins c-fynPyrimidinesAntibodies, MonoclonalBenzodioxolesDasatinibDimethyl SulfoxideDNA PrimersFYN protein, humanMycophenolic AcidProtein Kinase InhibitorsProto-Oncogene Proteins c-fynPyrimidinesQuinazolinesRNA, ViralsaracatinibThiazoles

Identifiers

PMID23616652
PMCPMC3700292
OpenAlexW2096314274

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.