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Article: Identification of influenza A nucleoprotein as an antiviral target

TitleIdentification of influenza A nucleoprotein as an antiviral target
Authors
KeywordsBiology
Biotechnology technology: comprehensive works medical sciences chemistry
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nbt
Citation
Nature Biotechnology, 2010, v. 28 n. 6, p. 600-605 How to Cite?
AbstractInfluenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly, creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC 50) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies. © 2010 Nature America, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/65450
ISSN
2015 Impact Factor: 43.113
2015 SCImago Journal Rankings: 18.932
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
Research Fund for the Control of Infectious Diseases
Area of Excellence Scheme of the University Grant CouncilAoE/M-12/06
Hong Kong Sanatorium Hospital Doctors' Donation Fund
Funding Information:

This study was supported in part by the Carol Yu Center for Infection Seed Fund for Basic Research from the University of Hong Kong, the Research Fund for the Control of Infectious Diseases and the Area of Excellence Scheme of the University Grant Council (Grant AoE/M-12/06). The Beckman Coulter Core system is a generous gift from the Hong Kong Sanatorium Hospital Doctors' Donation Fund by Y.-C. Tsao, C.-M. Chan, G. Lo, K.-M. Lai, R. K. Y. Lo, M. Tsao, B. S. S. Tse, T.-F. Tse, S. W. C. Wu, D. Y. C. Yu, R. Y. H. Yu and Y.-K. Tsao. We are grateful to R. Webster for gifts of the pHW2000 plasmids and E. Hoffmann for luciferase reporter system. We thank V. Poon, C. Chan and Q. Zhang for mice studies and K. H. Chan for virus strains. The use of Confocal Systems Core Facility provided by the LKS Faculty of Medicine, HKU, is acknowledged.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorKao, RYen_HK
dc.contributor.authorYang, Den_HK
dc.contributor.authorLau, LSen_HK
dc.contributor.authorTsui, WHWen_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorDai, Jen_HK
dc.contributor.authorChan, MPen_HK
dc.contributor.authorChan, CMen_HK
dc.contributor.authorWang, Pen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorSun, Jen_HK
dc.contributor.authorHuang, JDen_HK
dc.contributor.authorMadar, Jen_HK
dc.contributor.authorChen, Gen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorYuen, KYen_HK
dc.date.accessioned2010-08-09T01:17:17Z-
dc.date.available2010-08-09T01:17:17Z-
dc.date.issued2010en_HK
dc.identifier.citationNature Biotechnology, 2010, v. 28 n. 6, p. 600-605en_HK
dc.identifier.issn1087-0156en_HK
dc.identifier.urihttp://hdl.handle.net/10722/65450-
dc.description.abstractInfluenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains. Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly, creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC 50) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies. © 2010 Nature America, Inc. All rights reserved.en_HK
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nbten_HK
dc.relation.ispartofNature Biotechnologyen_HK
dc.subjectBiology-
dc.subjectBiotechnology technology: comprehensive works medical sciences chemistry-
dc.titleIdentification of influenza A nucleoprotein as an antiviral targeten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1087-0156&volume=28&issue=6&spage=600&epage=605&date=2010&atitle=Identification+of+influenza+A+nucleoprotein+as+an+antiviral+target-
dc.identifier.emailKao, RY: rytkao@hkucc.hku.hken_HK
dc.identifier.emailYang, D: yangdan@hku.hken_HK
dc.identifier.emailZheng, BJ: bzheng@hkucc.hku.hken_HK
dc.identifier.emailHuang, JD: jdhuang@hku.hken_HK
dc.identifier.emailChen, G: ghchen@hku.hken_HK
dc.identifier.emailChen, H: hlchen@hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityKao, RY=rp00481en_HK
dc.identifier.authorityYang, D=rp00825en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.identifier.authorityChen, G=rp00671en_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nbt.1638en_HK
dc.identifier.pmid20512121-
dc.identifier.scopuseid_2-s2.0-77953259427en_HK
dc.identifier.hkuros172428-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953259427&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume28en_HK
dc.identifier.issue6en_HK
dc.identifier.spage600en_HK
dc.identifier.epage605en_HK
dc.identifier.eissn1546-1696-
dc.identifier.isiWOS:000278820200024-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridKao, RY=7101675499en_HK
dc.identifier.scopusauthoridYang, D=7404800756en_HK
dc.identifier.scopusauthoridLau, LS=36515111800en_HK
dc.identifier.scopusauthoridTsui, WHW=36124344600en_HK
dc.identifier.scopusauthoridHu, L=7401557295en_HK
dc.identifier.scopusauthoridDai, J=36514300800en_HK
dc.identifier.scopusauthoridChan, MP=36514391000en_HK
dc.identifier.scopusauthoridChan, CM=7404814453en_HK
dc.identifier.scopusauthoridWang, P=13907209900en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridSun, J=7410369598en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK
dc.identifier.scopusauthoridMadar, J=36167041800en_HK
dc.identifier.scopusauthoridChen, G=35253368600en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.citeulike7289886-

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