tetano
Editor, Senior Moderator
Sci Rep. 2013;3:1106. doi: 10.1038/srep01106. Epub 2013 Jan 22.
A cell-based screening system for influenza A viral RNA transcription/replication inhibitors.
Ozawa M, Shimojima M, Goto H, Watanabe S, Hatta Y, Kiso M, Furuta Y, Horimoto T, Peters NR, Hoffmann FM, Kawaoka Y.
Source
Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo , Tokyo 108-8639, Japan ; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53711, USA ; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University , 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Abstract
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.
PMID:
23346363
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/23346363
A cell-based screening system for influenza A viral RNA transcription/replication inhibitors.
Ozawa M, Shimojima M, Goto H, Watanabe S, Hatta Y, Kiso M, Furuta Y, Horimoto T, Peters NR, Hoffmann FM, Kawaoka Y.
Source
Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo , Tokyo 108-8639, Japan ; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53711, USA ; Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University , 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Abstract
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.
PMID:
23346363
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/23346363