A cell-based screening system for influenza A viral RNA transcription/replication inhibitors

Although two classes of antivirals, NA inhibitors and M2 ion channel blockers, are licensed for influenza treatment, dual resistant mutants, including highly pathogenic H5N1 viruses, have appeared. Alternative treatment options are, therefore, needed. Influenza A viral RNA (vRNA) transcription/repli...

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Main Authors:	Ozawa, Makoto, Shimojima, Masayuki, Goto, Hideo, Watanabe, Shinji, Hatta, Yasuko, Kiso, Maki, Furuta, Yousuke, Horimoto, Taisuke, Peters, Noel R., Hoffmann, F. Michael, Kawaoka, Yoshihiro
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551287/

id	pubmed-3551287
recordtype	oai_dc
spelling	pubmed-35512872013-01-23 A cell-based screening system for influenza A viral RNA transcription/replication inhibitors Ozawa, Makoto Shimojima, Masayuki Goto, Hideo Watanabe, Shinji Hatta, Yasuko Kiso, Maki Furuta, Yousuke Horimoto, Taisuke Peters, Noel R. Hoffmann, F. Michael Kawaoka, Yoshihiro Article Although two classes of antivirals, NA inhibitors and M2 ion channel blockers, are licensed for influenza treatment, dual resistant mutants, including highly pathogenic H5N1 viruses, have appeared. Alternative treatment options are, therefore, needed. Influenza A viral RNA (vRNA) transcription/replication is a promising target for antiviral development, since it is essential for virus replication. Accordingly, an efficient and reliable method to identify vRNA transcription/replication inhibitors is desirable. Here, we developed a cell-based screening system by establishing a cell line that stably expresses influenza viral ribonucleoprotein complex (vRNP). Compound library screening using this cell line allowed us to identify a compound that inhibits vRNA transcription/replication by using reporter protein expression from virus-like RNA as a readout and virus replication in vitro. vRNP-expressing cells have potential as a simple and convenient high-throughput screening (HTS) system, and, thus, are promising to identify vRNA transcription/replication inhibitors for various RNA viruses, especially for primary screens. Nature Publishing Group 2013-01-22 /pmc/articles/PMC3551287/ /pubmed/23346363 http://dx.doi.org/10.1038/srep01106 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ozawa, Makoto Shimojima, Masayuki Goto, Hideo Watanabe, Shinji Hatta, Yasuko Kiso, Maki Furuta, Yousuke Horimoto, Taisuke Peters, Noel R. Hoffmann, F. Michael Kawaoka, Yoshihiro
spellingShingle	Ozawa, Makoto Shimojima, Masayuki Goto, Hideo Watanabe, Shinji Hatta, Yasuko Kiso, Maki Furuta, Yousuke Horimoto, Taisuke Peters, Noel R. Hoffmann, F. Michael Kawaoka, Yoshihiro A cell-based screening system for influenza A viral RNA transcription/replication inhibitors
author_facet	Ozawa, Makoto Shimojima, Masayuki Goto, Hideo Watanabe, Shinji Hatta, Yasuko Kiso, Maki Furuta, Yousuke Horimoto, Taisuke Peters, Noel R. Hoffmann, F. Michael Kawaoka, Yoshihiro
author_sort	Ozawa, Makoto
title	A cell-based screening system for influenza A viral RNA transcription/replication inhibitors
title_short	A cell-based screening system for influenza A viral RNA transcription/replication inhibitors
title_full	A cell-based screening system for influenza A viral RNA transcription/replication inhibitors
title_fullStr	A cell-based screening system for influenza A viral RNA transcription/replication inhibitors
title_full_unstemmed	A cell-based screening system for influenza A viral RNA transcription/replication inhibitors
title_sort	cell-based screening system for influenza a viral rna transcription/replication inhibitors
description	Although two classes of antivirals, NA inhibitors and M2 ion channel blockers, are licensed for influenza treatment, dual resistant mutants, including highly pathogenic H5N1 viruses, have appeared. Alternative treatment options are, therefore, needed. Influenza A viral RNA (vRNA) transcription/replication is a promising target for antiviral development, since it is essential for virus replication. Accordingly, an efficient and reliable method to identify vRNA transcription/replication inhibitors is desirable. Here, we developed a cell-based screening system by establishing a cell line that stably expresses influenza viral ribonucleoprotein complex (vRNP). Compound library screening using this cell line allowed us to identify a compound that inhibits vRNA transcription/replication by using reporter protein expression from virus-like RNA as a readout and virus replication in vitro. vRNP-expressing cells have potential as a simple and convenient high-throughput screening (HTS) system, and, thus, are promising to identify vRNA transcription/replication inhibitors for various RNA viruses, especially for primary screens.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551287/
_version_	1611948543096913920

A cell-based screening system for influenza A viral RNA transcription/replication inhibitors

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