Evidence map›Paper›PMID 24663025›Full record

ArticleAntimicrobial agents and chemotherapy2014

Inhibitors of the tick-borne, hemorrhagic fever-associated flaviviruses.

Mike Flint, Laura K McMullan, Kimberly A Dodd, Brian H Bird, Marina L Khristova, Stuart T Nichol, Christina F Spiropoulou

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Molecules (Basel, Switzerland) · 2024
    Review
  5. Powassan Virus Encephalitis.Infectious disease clinics of North America · 2022
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. TMEM41B is a pan-flavivirus host factor.bioRxiv : the preprint server for biology · 2020
    Article
  11. Article
  12. Article
  13. Viral RNA-Dependent RNA Polymerase Inhibitor 7-Deaza-2'-Antimicrobial agents and chemotherapy · 2019
    Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Escape of Tick-Borne Flavivirus from 2'-Journal of virology · 2017
    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 1 institution in 1 country.

Mike FlintViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Laura K McMullanViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Kimberly A DoddViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA University of California Davis, School of Veterinary Medicine, Davis, California, USA.
Brian H BirdViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Marina L KhristovaViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Stuart T NicholViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Christina F SpiropoulouViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA ccs8@cdc.gov.
Centers for Disease Control and Prevention · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

No antiviral therapies are available for the tick-borne flaviviruses associated with hemorrhagic fevers: Kyasanur Forest disease virus (KFDV), both classical and the Alkhurma hemorrhagic fever virus (AHFV) subtype, and Omsk hemorrhagic fever virus (OHFV). We tested compounds reported to have antiviral activity against members of the Flaviviridae family for their ability to inhibit AHFV replication. 6-Azauridine (6-azaU), 2'-C-methylcytidine (2'-CMC), and interferon alpha 2a (IFN-α2a) inhibited the replication of AHFV and also KFDV, OHFV, and Powassan virus. The combination of IFN-α2a and 2'-CMC exerted an additive antiviral effect on AHFV, and the combination of IFN-α2a and 6-azaU was moderately synergistic. The combination of 2'-CMC and 6-azaU was complex, being strongly synergistic but with a moderate level of antagonism. The antiviral activity of 6-azaU was reduced by the addition of cytidine but not guanosine, suggesting that it acted by inhibiting pyrimidine biosynthesis. To investigate the mechanism of action of 2'-CMC, AHFV variants with reduced susceptibility to 2'-CMC were selected. We used a replicon system to assess the substitutions present in the selected AHFV population. A double NS5 mutant, S603T/C666S, and a triple mutant, S603T/C666S/M644V, were more resistant to 2'-CMC than the wild-type replicon. The S603T/C666S mutant had a reduced level of replication which was increased when M644V was also present, although the replication of this triple mutant was still below that of the wild type. The S603 and C666 residues were predicted to lie in the active site of the AHFV NS5 polymerase, implicating the catalytic center of the enzyme as the binding site for 2'-CMC.

Indexed as

Amino Acid SubstitutionAntiviral AgentsCell LineCytidineCytopathogenic Effect, ViralDrug Resistance, ViralFlavivirusHemorrhagic Fevers, ViralHumansModels, MolecularMutationTick-Borne DiseasesVirus Replication2'-C-methylcytidineAntiviral AgentsCytidine

Identifiers

PMID24663025
PMCPMC4068503
OpenAlexW2114622167

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.