Evidence map›Paper›PMID 26976570›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Spironolactone blocks Epstein-Barr virus production by inhibiting EBV SM protein function.

Dinesh Verma, Jacob Thompson, Sankar Swaminathan

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
1.9field-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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

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

3 authors at 1 institution in 1 country.

Dinesh VermaDivision of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132.
Jacob ThompsonDivision of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132.
Sankar SwaminathanDivision of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132 sankar.swaminathan@hsc.utah.edu.
University of Utah · US

Funding

POSTTRANSCRIPTIONAL GENE REGULATION BY EBV SM PROTEINR01CA081133 · NCI · UNIVERSITY OF UTAH · PI SWAMINATHAN, SANKAR · 1999 to 2022
$4.9M
NCI NIH HHS R01 CA081133PHS HHS R01 81133
6 · The paper itself

Abstract

Clinically available drugs active against Epstein-Barr virus (EBV) and other human herpesviruses are limited to those targeting viral DNA replication. To identify compounds directed against other steps in the viral life cycle, we searched for drugs active against the EBV SM protein, which is essential for infectious virus production. SM has a highly gene-specific mode of action and preferentially enhances expression of several late lytic cycle EBV genes. Here we demonstrate that spironolactone, a mineralocorticoid receptor antagonist approved for clinical use, inhibits SM function and infectious EBV production. Expression of EBV viral capsid antigen is highly SM dependent, and spironolactone inhibits viral capsid antigen synthesis and capsid formation, blocking EBV virion production at a step subsequent to viral DNA replication. In addition, spironolactone inhibits expression of other SM-dependent genes necessary for infectious virion formation. We further demonstrate that molecules structurally related to spironolactone with similar antimineralocorticoid blocking activity do not inhibit EBV production. These findings pave the way for development of antiherpesvirus drugs with new mechanisms of action directed against SM and homologous essential proteins in other herpesviruses.

Indexed as

Antiviral AgentsCapsid ProteinsCell LineDNA ReplicationGene DeletionGene Expression Regulation, ViralGene Knockout TechniquesGenes, ViralHEK293 CellsHerpesvirus 4, HumanHumansImmediate-Early ProteinsMineralocorticoid Receptor AntagonistsSpironolactoneStructure-Activity RelationshipTrans-ActivatorsAntiviral AgentsBRLF1 protein, Human herpesvirus 4Capsid ProteinsImmediate-Early ProteinsMineralocorticoid Receptor AntagonistsSpironolactoneTrans-ActivatorsantiviralEpstein–Barr virusherpesvirusposttranscriptional regulationspironolactone

Identifiers

PMID26976570
PMCPMC4822607
OpenAlexW2299952845

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.