Evidence map›Paper›PMID 23824813›Full record

ArticleJournal of virology2013

Flaviviruses are sensitive to inhibition of thymidine synthesis pathways.

Matthew A Fischer, Jessica L Smith, David Shum, David A Stein, Christopher Parkins, Bhavneet Bhinder, Constantin Radu, Alec J Hirsch, Hakim Djaballah, Jay A Nelson and 1 more

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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

17 citing papers in PubMed, 34 citations in OpenAlex.

  1. Repurposing of the nucleoside analogs for influenza.Computational and structural biotechnology journal · 2025
    Article
  2. Review
  3. Article
  4. Article
  5. Drugs for the Treatment of Zika Virus Infection.Journal of medicinal chemistry · 2020
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. A Roadmap for Tick-Borne Flavivirus Research in the "Omics" Era.Frontiers in cellular and infection microbiology · 2017
    Review
  14. Article
  15. Article
  16. Article
  17. Review
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

11 authors at 3 institutions in 1 country.

Matthew A FischerVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA.
Jessica L Smith
David Shum
David A Stein
Christopher Parkins
Bhavneet Bhinder
Constantin Radu
Alec J Hirsch
Hakim Djaballah
Jay A Nelson
Klaus Früh
Oregon Health & Science University · USNew York Structural Biology Center · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
The Burden of Chikungunya and Dengue Infection in KenyaU54AI081680 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI GALLOWAY, DENISE A. · 2009 to 2013
$40.4M
INTERACTIONS AT THE MICROBE/HOST INTERFACET32AI007472 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI LANDFEAR, SCOTT M · 1995 to 2019
$6.7M
Training Program in VirologyT32AI074494 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI NELSON, JAY A · 2009 to 2013
$1.1M
NCI NIH HHS 5 P30 CA008748-44NCI NIH HHS P30 CA008748NIAID NIH HHS T32 AI007472NIAID NIH HHS T32 AI074494NIAID NIH HHS T32 AI07472NIAID NIH HHS U54 AI 081680NIAID NIH HHS U54 AI081680NIH HHS 8P51 OD011092-54NIH HHS P51 OD011092
6 · The paper itself

Abstract

Dengue virus has emerged as a global health threat to over one-third of humankind. As a positive-strand RNA virus, dengue virus relies on the host cell metabolism for its translation, replication, and egress. Therefore, a better understanding of the host cell metabolic pathways required for dengue virus infection offers the opportunity to develop new approaches for therapeutic intervention. In a recently described screen of known drugs and bioactive molecules, we observed that methotrexate and floxuridine inhibited dengue virus infections at low micromolar concentrations. Here, we demonstrate that all serotypes of dengue virus, as well as West Nile virus, are highly sensitive to both methotrexate and floxuridine, whereas other RNA viruses (Sindbis virus and vesicular stomatitis virus) are not. Interestingly, flavivirus replication was restored by folinic acid, a thymidine precursor, in the presence of methotrexate and by thymidine in the presence of floxuridine, suggesting an unexpected role for thymidine in flavivirus replication. Since thymidine is not incorporated into RNA genomes, it is likely that increased thymidine production is indirectly involved in flavivirus replication. A possible mechanism is suggested by the finding that p53 inhibition restored dengue virus replication in the presence of floxuridine, consistent with thymidine-less stress triggering p53-mediated antiflavivirus effects in infected cells. Our data reveal thymidine synthesis pathways as new and unexpected therapeutic targets for antiflaviviral drug development.

Indexed as

AnimalsAntiviral AgentsCell LineChlorocebus aethiopsDengue VirusDisease Models, AnimalDNA VirusesFlavivirusFlavivirus InfectionsFloxuridineHEK293 CellsHeLa CellsHumansLeucovorinMethotrexateMiceAntiviral AgentsFloxuridineLeucovorinMethotrexateThymidineTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID23824813
PMCPMC3754125
OpenAlexW2070598999

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.