Evidence map›Paper›PMID 27956134›Full record

ArticleAntiviral research2017

Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins.

Rooksarr Beelontally, Gavin S Wilkie, Betty Lau, Charles J Goodmaker, Catherine M K Ho, Chad M Swanson, Xianming Deng, Jinhua Wang, Nathanael S Gray, Andrew J Davison and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Antiviral research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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

11 authors at 4 institutions in 2 countries.

Rooksarr BeelontallyInstitute of Infection & Immunity, St George's, University of London, London, UK.
Gavin S WilkieMRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
Betty LauMRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
Charles J GoodmakerInstitute of Infection & Immunity, St George's, University of London, London, UK.
Catherine M K HoInstitute of Infection & Immunity, St George's, University of London, London, UK.
Chad M SwansonDepartment of Infectious Diseases, King's College London, London, UK.
Xianming DengDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jinhua WangDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nathanael S GrayDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Andrew J DavisonMRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
Blair L StrangInstitute of Infection & Immunity, St George's, University of London, London, UK; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. Electronic address: bstrang@sgul.ac.uk.
Harvard University · USMRC University of Glasgow Centre for Virus Research · GBSt George's, University of London · GBKing's College London · GB

Funding

Human Cytomegalovirus Nuclear Egress: Molecular Mechanisms and Drug TargetingR01AI026077 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI COEN, DONALD M · 1999 to 2019
$10.9M
MOLECULAR GENETICS OF HSV DNA POLYMERASE GENER01AI019838 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI COEN, DONALD M, HOGLE, JAMES M · 1985 to 2015
$5.9M
Medical Research Council MC_UU_12014/12Medical Research Council MC_UU_12014/3Medical Research Council MR/K000381/1Medical Research Council MR/M019756/1NIAID NIH HHS R01 AI019838NIAID NIH HHS R01 AI026077
6 · The paper itself

Abstract

Using a high throughput screening methodology we surveyed a collection of largely uncharacterized validated or suspected kinase inhibitors for anti-human cytomegalovirus (HCMV) activity. From this screen we identified three structurally related 5-aminopyrazine compounds (XMD7-1, -2 and -27) that inhibited HCMV replication in virus yield reduction assays at low micromolar concentrations. Kinase selectivity assays indicated that each compound was a kinase inhibitor capable of inhibiting a range of cellular protein kinases. Western blotting and RNA sequencing demonstrated that treatment of infected cells with XMD7 compounds resulted in a defect in the production of the major HCMV transcriptional transactivator IE2 proteins (IE2-86, IE2-60 and IE2-40) and an overall reduction in transcription from the viral genome. However, production of certain viral proteins was not compromised by treatment with XMD7 compounds. Thus, these novel anti-HCMV compounds likely inhibited transcription from the viral genome and suppressed production of a subset of viral proteins by inhibiting IE2 protein production.

Indexed as

Drug DiscoveryAntiviral AgentsCell LineCytomegalovirusDNA ReplicationHigh-Throughput Screening AssaysHumansImmediate-Early ProteinsTrans-ActivatorsTranscription, GeneticViral ProteinsVirus ReplicationAntiviral AgentsIE2 protein, CytomegalovirusImmediate-Early ProteinsTrans-ActivatorsViral ProteinsCompoundHuman cytomegalovirusIE2InhibitorKinaseScreen

Identifiers

PMID27956134
PMCPMC5244968
OpenAlexW2560843563

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.