Evidence map›Paper›PMID 24518064›Full record

ArticleJournal of biomolecular screening2014

Assay Development and High-Throughput Screening for Inhibitors of Kaposi's Sarcoma-Associated Herpesvirus N-Terminal Latency-Associated Nuclear Antigen Binding to Nucleosomes.

Chantal Beauchemin, Nathan J Moerke, Patrick Faloon, Kenneth M Kaye

Open access · hybridAbstract read
In one paragraph

Article in Journal of biomolecular screening, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  3. Microscale Thermophoresis Analysis of Chromatin Interactions.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  4. Article
  5. Article
  6. Potent Activation of NADACS chemical biology · 2022
    Article
  7. Discovery of small-molecule inhibitors of multidrug-resistance plasmid maintenance using a high-throughput screening approach.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  8. Article
  9. Article
  10. Review
  11. Site-Specific Studies of Nucleosome Interactions by Solid-State NMR Spectroscopy.Angewandte Chemie (International ed. in English) · 2018
    Article
  12. Article
  13. Kaposi's Sarcoma Herpesvirus Genome Persistence.Frontiers in microbiology · 2016
    Review
  14. 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

4 authors at 3 institutions in 1 country.

Chantal BeaucheminDepartments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nathan J MoerkeDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Patrick FaloonBroad Institute, Center for the Science of Therapeutics, Therapeutics Platform, Cambridge, USA.
Kenneth M KayeDepartments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA kkaye@rics.bwh.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USBroad Institute · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KASPER, DENNIS L. · 2003 to 2013
$113.7M
User Driven ProjectU54HG005032 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SCHREIBER, STUART L · 2008 to 2013
$88.1M
GENETIC AND BIOCHEMICAL STUDIES OF THE KSHV LANA GENER01CA082036 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KAYE, KENNETH M · 1999 to 2019
$7.6M
Chemical Probes of Kaposi's Sarcoma Herpesvirus Latent InfectionR21NS061738 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KAYE, KENNETH M · 2007 to 2010
$220k
CIHRNCI NIH HHS CA082036NCI NIH HHS R01 CA082036NHGRI NIH HHS 5U54HG005032NHGRI NIH HHS U54 HG005032NIAID NIH HHS U54 AI057159NINDS NIH HHS R21 NS061738NINDS NIH HHS R21 NS061738-01
6 · The paper itself

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies, especially in immunocompromised hosts. KSHV latently infects tumor cells and persists as an extrachromosomal episome (plasmid). KSHV latency-associated nuclear antigen (LANA) mediates KSHV episome persistence. LANA binds specific KSHV sequence to replicate viral DNA. In addition, LANA tethers KSHV genomes to mitotic chromosomes to efficiently segregate episomes to daughter nuclei after mitosis. N-terminal LANA (N-LANA) binds histones H2A and H2B to attach to chromosomes. Currently, there are no specific inhibitors of KSHV latent infection. To enable high-throughput screening (HTS) of inhibitors of N-LANA binding to nucleosomes, here we develop, miniaturize, and validate a fluorescence polarization (FP) assay that detects fluorophore-labeled N-LANA peptide binding to nucleosomes. We also miniaturize a counterscreen to identify DNA intercalators that nonspecifically inhibit N-LANA binding to nucleosomes, and also develop an enzyme-linked immunosorbent assay to assess N-LANA binding to nucleosomes in the absence of fluorescence. HTS of libraries containing more than 350,000 compounds identified multiple compounds that inhibited N-LANA binding to nucleosomes. No compounds survived all counterscreens, however. More complex small-molecule libraries will likely be necessary to identify specific inhibitors of N-LANA binding to histones H2A and H2B; these assays should prove useful for future screens.

Indexed as

AnimalsAntigensAntigens, ViralAntiviral AgentsCell SurvivalChickensDrug DesignEnzyme-Linked Immunosorbent AssayErythrocytesFluorescence PolarizationFluorescent DyesGlutathione TransferaseHeLa CellsHerpesvirus 8, HumanHigh-Throughput Screening AssaysHistonesAntigensAntigens, ViralAntiviral AgentsFluorescent DyesGlutathione TransferaseHistoneslatency-associated nuclear antigenNuclear ProteinsNucleosomesepisomeKaposi’s sarcoma–associated herpesvirus (KSHV)latency-associated nuclear antigen (LANA)

Identifiers

PMID24518064
PMCPMC4656118
OpenAlexW2102917986

What OpenQuestion holds

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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.