Evidence map›Paper›PMID 31711927›Full record

ArticleAntiviral research2020

Small molecule screening identifies inhibitors of the Epstein-Barr virus deubiquitinating enzyme, BPLF1.

Sage L Atkins, Safiyyah Motaib, Laura C Wiser, Sharon E Hopcraft, Paul B Hardy, Julia Shackelford, Peter Foote, Ashley H Wade, Blossom Damania, Joseph S Pagano and 2 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antiviral research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

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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

12 authors at 2 institutions in 1 country.

Sage L AtkinsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Safiyyah MotaibLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laura C WiserLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sharon E HopcraftLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Paul B HardyEshelman School of Pharmacy, Center for Integrative Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Julia ShackelfordLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Peter FooteLife Sensors Inc, Malvern, PA, USA.
Ashley H WadeLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Blossom DamaniaLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Joseph S PaganoLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kenneth H PearceEshelman School of Pharmacy, Center for Integrative Biology and Drug Discovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Christopher B WhitehurstLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: cbwhiteh@med.unc.edu.
University of North Carolina at Chapel Hill · USLifeSensors (United States) · US

Funding

Vironomics and Biostatistics CoreP01CA019014 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLOSSOM A DAMANIA, NANCY JOAN RAAB-TRAUB · 1985 to 2026
$43.8M
Role of KSHV Viral Proteins in Signaling and PathogenesisR01CA096500 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAMANIA, BLOSSOM A · 2002 to 2022
$6.0M
NCI NIH HHS P01 CA019014NCI NIH HHS R01 CA096500
6 · The paper itself

Abstract

Herpesviral deubiquitinating enzymes (DUBs) were discovered in 2005, are highly conserved across the family, and are proving to be increasingly important players in herpesviral infection. EBV's DUB, BPLF1, is known to regulate both cellular and viral target activities, yet remains largely unstudied. Our work has implicated BPLF1 in a wide range of processes including infectivity, viral DNA replication, and DNA repair. Additionally, knockout of BPLF1 delays and reduces human B-cell immortalization and lymphoma formation in humanized mice. These findings underscore the importance of BPLF1 in viral infectivity and pathogenesis and suggest that inhibition of EBV's DUB activity may offer a new approach to specific therapy for EBV infections. We set out to discover and characterize small molecule inhibitors of BPLF1 deubiquitinating activity through high-throughput screening. An initial small pilot screen resulted in discovery of 10 compounds yielding >80% decrease in BPLF1 DUB activity at a 10 μM concentration. Follow-up dose response curves of top hits identified several compounds with an IC

Indexed as

Drug Evaluation, PreclinicalAntiviral AgentsCell SurvivalDeubiquitinating EnzymesDose-Response Relationship, DrugHEK293 CellsHerpesvirus 4, HumanHigh-Throughput Screening AssaysHumansSmall Molecule LibrariesViral Regulatory and Accessory ProteinsVirus ReplicationAntiviral AgentsBPLF1 protein, Epstein-Barr virusDeubiquitinating EnzymesSmall Molecule LibrariesViral Regulatory and Accessory ProteinsAntiviralBPLF1Deubiquitinating enzymeDrug screenDUBEpstein-Barr virusHerpesvirusORF64Suramin

Identifiers

PMID31711927
PMCPMC7017600
OpenAlexW2983243108

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.