Evidence map›Paper›PMID 28819179›Full record

ArticleScientific reports2017

Identification of Polo-like kinases as potential novel drug targets for influenza A virus.

Marie O Pohl, Jessica von Recum-Knepper, Ariel Rodriguez-Frandsen, Caroline Lanz, Emilio Yángüez, Stephen Soonthornvacharin, Thorsten Wolff, Sumit K Chanda, Silke Stertz

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

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  4. Review
  5. 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

9 authors at 3 institutions in 4 countries.

Marie O PohlInstitute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Jessica von Recum-KnepperImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Ariel Rodriguez-FrandsenImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Caroline LanzInstitute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Emilio YángüezInstitute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Stephen SoonthornvacharinImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Thorsten WolffUnit 17, Influenza and Other Respiratory Viruses, Robert Koch Institute, 13353, Berlin, Germany.ORCID 0000-0001-7688-236X
Sumit K ChandaImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Silke StertzInstitute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. stertz.silke@virology.uzh.ch.
Sanford Burnham Prebys Medical Discovery Institute · USUniversity of Zurich · CHRobert Koch Institute · DE

Funding

Virus CoreU19AI106754 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DENNIS, EDWARD A · 2013 to 2017
$26.0M
NIAID NIH HHS U19 AI106754
6 · The paper itself

Abstract

In recent years genome-wide RNAi screens have revealed hundreds of cellular factors required for influenza virus infections in human cells. The long-term goal is to establish some of them as drug targets for the development of the next generation of antivirals against influenza. We found that several members of the polo-like kinases (PLK), a family of serine/threonine kinases with well-known roles in cell cycle regulation, were identified as hits in four different RNAi screens and we therefore studied their potential as drug target for influenza. We show that knockdown of PLK1, PLK3, and PLK4, as well as inhibition of PLK kinase activity by four different compounds, leads to reduced influenza virus replication, and we map the requirement of PLK activity to early stages of the viral replication cycle. We also tested the impact of the PLK inhibitor BI2536 on influenza virus replication in a human lung tissue culture model and observed strong inhibition of virus replication with no measurable toxicity. This study establishes the PLKs as potential drug targets for influenza and contributes to a more detailed understanding of the intricate interactions between influenza viruses and their host cells.

Indexed as

A549 CellsAnimalsAntimitotic AgentsCell Cycle ProteinsDogsGlycineHEK293 CellsHumansInfluenza A virusInfluenza, HumanMadin Darby Canine Kidney CellsPolo-Like Kinase 1Polo-like KinasesProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsAntimitotic AgentsBI 2536Cell Cycle ProteinsGlycineON 01910PLK3 protein, humanPLK4 protein, humanPolo-Like Kinase 1Polo-like KinasesProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsPteridinesSulfonesTumor Suppressor Proteins

Identifiers

PMID28819179
PMCPMC5561215
OpenAlexW2745284772

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.