Evidence map›Paper›PMID 20930215›Full record

ArticleJournal of biomolecular screening2010

Development of a high-throughput screen for inhibitors of Epstein-Barr virus EBNA1.

Scott Thompson, Troy Messick, David C Schultz, Melvin Reichman, Paul M Lieberman

Open access · hybridAbstract read
In one paragraph

Article in Journal of biomolecular screening, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

31 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Cytokine Storm Syndromes Associated with Epstein-Barr Virus.Advances in experimental medicine and biology · 2024
    Review
  6. Review
  7. How Does Epstein-Barr Virus Interact With Other Microbiomes in EBV-Driven Cancers?Frontiers in cellular and infection microbiology · 2022
    Review
  8. Review
  9. Review
  10. Review
  11. A Broad Application of CRISPR Cas9 in Infectious Diseases of Central Nervous System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019
    Review
  12. Article
  13. Review
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  15. Review
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  18. Article
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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.

Scott ThompsonThe Wistar Institute, Philadelphia, PA 19104, USA.
Troy Messick
David C Schultz
Melvin Reichman
Paul M Lieberman
The Wistar Institute · US

Funding

Assay For Inhibitors of Epstein-Barr VirusR21NS063906 · NINDS · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2008 to 2009
$193k
NINDS NIH HHS 3R21NS063906NINDS NIH HHS R21 NS063906Wellcome Trust 096496
6 · The paper itself

Abstract

Latent infection with Epstein-Barr virus (EBV) is a carcinogenic cofactor in several lymphoid and epithelial cell malignancies. At present, there are no small-molecule inhibitors that specifically target EBV latent infection or latency-associated oncoproteins. EBNA1 is an EBV-encoded sequence-specific DNA binding protein that is consistently expressed in EBV-associated tumors and required for stable maintenance of the viral genome in proliferating cells. EBNA1 is also thought to provide cell survival function in latently infected cells. In this work, the authors describe the development of a biochemical high-throughput screening (HTS) method using a homogeneous fluorescence polarization (FP) assay monitoring EBNA1 binding to its cognate DNA binding site. An FP-based counterscreen was developed using another EBV-encoded DNA binding protein, Zta, and its cognate DNA binding site. The authors demonstrate that EBNA1 binding to a fluorescent-labeled DNA probe provides a robust assay with a Z factor consistently greater than 0.6. A pilot screen of a small-molecule library of ~14,000 compounds identified 3 structurally related molecules that selectively inhibit EBNA1 but not Zta. All 3 compounds had activity in a cell-based assay specific for the disruption of EBNA1 transcription repression function. One of the compounds was effective in reducing EBV genome copy number in Raji Burkitt lymphoma cells. These experiments provide a proof of concept that small-molecule inhibitors of EBNA1 can be identified by biochemical HTS of compound libraries. Further screening in conjunction with medicinal chemistry optimization may provide a selective inhibitor of EBNA1 and EBV latent infection.

Indexed as

Cell Line, TumorDNAElectrophoretic Mobility Shift AssayEpstein-Barr Virus Nuclear AntigensFluorescence PolarizationGene DosageHerpesvirus 4, HumanHigh-Throughput Screening AssaysHumansInhibitory Concentration 50PlasmidsProtein BindingSmall Molecule LibrariesTrans-ActivatorsTranscription, GeneticBZLF1 protein, Herpesvirus 4, HumanDNAEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensSmall Molecule LibrariesTrans-Activators

Identifiers

PMID20930215
PMCPMC3310380
OpenAlexW2119446216

What OpenQuestion holds

Textmetadata
LicenceTDM
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.