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dc.contributor.author
Pohl, Marie O.
dc.contributor.author
Von Recum-Knepper, Jessica
dc.contributor.author
Rodriguez-Frandsen, Ariel
dc.contributor.author
Lanz, Caroline
dc.contributor.author
Yángüez, Emilio
dc.contributor.author
Soonthornvacharin, Stephen
dc.contributor.author
Wolff, Thorsten
dc.contributor.author
Chanda, Sumit K.
dc.contributor.author
Stertz, Silke
dc.date.accessioned
2017-11-13T12:15:52Z
dc.date.available
2017-10-06T02:52:48Z
dc.date.available
2017-11-13T12:15:52Z
dc.date.issued
2017
dc.identifier.other
10.1038/s41598-017-08942-7
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/191126
dc.identifier.doi
10.3929/ethz-b-000191126
dc.description.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.
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Identification of Polo-like kinases as potential novel drug targets for influenza A virus
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-08-17
ethz.journal.title
Scientific Reports
ethz.journal.volume
7
en_US
ethz.pages.start
8629
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-10-06T02:53:09Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-11-13T12:16:00Z
ethz.rosetta.lastUpdated
2019-01-02T10:43:42Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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