Evidence map›Paper›PMID 20881091›Full record

ArticleThe Journal of general virology2011

Novel inhibitor of influenza non-structural protein 1 blocks multi-cycle replication in an RNase L-dependent manner.

Marcin P Walkiewicz, Dipanwita Basu, Joseph J Jablonski, H Mario Geysen, Daniel A Engel

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of general virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  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

5 authors at 1 institution in 1 country.

Marcin P WalkiewiczDepartment of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Dipanwita Basu
Joseph J Jablonski
H Mario Geysen
Daniel A Engel
University of Virginia · US

Funding

Development of Yeast-Based Assays for anti-influenza drug discoveryR01AI071341 · NIAID · UNIVERSITY OF VIRGINIA · PI ENGEL, DANIEL A · 2006 to 2006
$666k
NIAID NIH HHS R01 AI071341NIAID NIH HHS R01AI071341
6 · The paper itself

Abstract

Influenza virus non-structural protein 1 (NS1) is the centrepiece of the viral response to the host interferon (IFN) system. NS1 has been demonstrated previously to be a potential therapeutic target for antiviral therapy by identification of specific small-molecule inhibitors. This study demonstrated the biological mechanism for a potent new NS1 antagonist. Compound JJ3297 inhibited virus replication by more than three orders of magnitude without affecting cell viability. Importantly, it efficiently reversed NS1-induced inhibition of IFN mRNA production. The hypothesis was tested that JJ3297 facilitates IFN production in infected cells, leading to protection of the surrounding uninfected cells. Accordingly, the compound efficiently prevented virus spread through a cell population during a 48 h multi-cycle infection initiated at a very low m.o.i. Consistent with the hypothesis, the compound had no detectable influence on a 6 h single-cycle infection initiated at a high m.o.i. The effect of JJ3297 on virus replication was not caused by inhibition of NS1 expression or its mislocalization in the cell. JJ3297 facilitated the induction of an IFN-like antiviral state, resulting in increased resistance to subsequent challenge with vesicular stomatitis virus. The activity of JJ3297 absolutely required the function of cellular RNase L, indicating that an intact IFN system is required for function of the compound. These results support a model in which inhibition of NS1 function results in restoration of the IFN-induced antiviral state and inhibition of virus replication and spread. This represents a new direction for anti-influenza virus drug development that exploits the IFN pathway to challenge virus replication.

Indexed as

AnimalsAntiviral AgentsCell LineDogsEndoribonucleasesInterferonsOrthomyxoviridaeVesiculovirusViral Nonstructural ProteinsVirus Replication2-5A-dependent ribonucleaseAntiviral AgentsEndoribonucleasesINS1 protein, influenza virusInterferonsViral Nonstructural Proteins

Identifiers

PMID20881091
PMCPMC3052532
OpenAlexW2106525727

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.