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

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 th...

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Autores principales:	Marie O. Pohl, Jessica von Recum-Knepper, Ariel Rodriguez-Frandsen, Caroline Lanz, Emilio Yángüez, Stephen Soonthornvacharin, Thorsten Wolff, Sumit K. Chanda, Silke Stertz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e32cf9c0d02e4584918dacbc8b49c6cb
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spelling	oai:doaj.org-article:e32cf9c0d02e4584918dacbc8b49c6cb2021-12-02T15:06:12ZIdentification of Polo-like kinases as potential novel drug targets for influenza A virus10.1038/s41598-017-08942-72045-2322https://doaj.org/article/e32cf9c0d02e4584918dacbc8b49c6cb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08942-7https://doaj.org/toc/2045-2322Abstract 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.Marie O. PohlJessica von Recum-KnepperAriel Rodriguez-FrandsenCaroline LanzEmilio YángüezStephen SoonthornvacharinThorsten WolffSumit K. ChandaSilke StertzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marie O. Pohl Jessica von Recum-Knepper Ariel Rodriguez-Frandsen Caroline Lanz Emilio Yángüez Stephen Soonthornvacharin Thorsten Wolff Sumit K. Chanda Silke Stertz Identification of Polo-like kinases as potential novel drug targets for influenza A virus
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.
format	article
author	Marie O. Pohl Jessica von Recum-Knepper Ariel Rodriguez-Frandsen Caroline Lanz Emilio Yángüez Stephen Soonthornvacharin Thorsten Wolff Sumit K. Chanda Silke Stertz
author_facet	Marie O. Pohl Jessica von Recum-Knepper Ariel Rodriguez-Frandsen Caroline Lanz Emilio Yángüez Stephen Soonthornvacharin Thorsten Wolff Sumit K. Chanda Silke Stertz
author_sort	Marie O. Pohl
title	Identification of Polo-like kinases as potential novel drug targets for influenza A virus
title_short	Identification of Polo-like kinases as potential novel drug targets for influenza A virus
title_full	Identification of Polo-like kinases as potential novel drug targets for influenza A virus
title_fullStr	Identification of Polo-like kinases as potential novel drug targets for influenza A virus
title_full_unstemmed	Identification of Polo-like kinases as potential novel drug targets for influenza A virus
title_sort	identification of polo-like kinases as potential novel drug targets for influenza a virus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e32cf9c0d02e4584918dacbc8b49c6cb
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Identification of Polo-like kinases as potential novel drug targets for influenza A virus

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