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Article: DAS181 inhibits H5N1 influenza virus infection of human lung tissues

TitleDAS181 inhibits H5N1 influenza virus infection of human lung tissues
Authors
Issue Date2009
PublisherAmerican Society for Microbiology.
Citation
Antimicrobial Agents And Chemotherapy, 2009, v. 53 n. 9, p. 3935-3941 How to Cite?
Abstract
DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both α2-6-linked and α2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1. Copyright © 2009, American Society for Microbiology.
Persistent Identifierhttp://hdl.handle.net/10722/79018
ISSN
2013 Impact Factor: 4.451
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
NIHHHSN266200600015C
1U01AI070281
Hong Kong GovernmentRFCID08070842
University Grants Committee of the Hong Kong Special Administrative Region, ChinaAoE/M-12/06
NIH NIAIDHHSN266200600015C
Wellcome Trust082098
BBSRC
CERG773507M
Funding Information:

This study was supported in part by NIH contracts HHSN266200600015C and 1U01AI070281, grant RFCID08070842 from the Hong Kong Government, and CERG773507M and the Area of Excellence program on influenza supported by the University Grants Committee of the Hong Kong Special Administrative Region, China ( project AoE/M-12/06). The work at NexBio was supported in part by NIH NIAID contract HHSN266200600015C. S. M. H. and A. D. acknowledge the support of the Wellcome Trust ( grant 082098) and the BBSRC.

References
Grants

 

Author Affiliations
  1. The University of Hong Kong
  2. NexBio, Inc.
  3. Imperial College London
DC FieldValueLanguage
dc.contributor.authorChan, RWYen_HK
dc.contributor.authorChan, MCWen_HK
dc.contributor.authorWong, ACNen_HK
dc.contributor.authorKaramanska, Ren_HK
dc.contributor.authorDell, Aen_HK
dc.contributor.authorHaslam, SMen_HK
dc.contributor.authorSihoe, ADLen_HK
dc.contributor.authorChui, WHen_HK
dc.contributor.authorTrianaBaltzer, Gen_HK
dc.contributor.authorLi, Qen_HK
dc.contributor.authorMalik Peiris, JSen_HK
dc.contributor.authorFang, Fen_HK
dc.contributor.authorNicholls, JMen_HK
dc.date.accessioned2010-09-06T07:49:35Z-
dc.date.available2010-09-06T07:49:35Z-
dc.date.issued2009en_HK
dc.identifier.citationAntimicrobial Agents And Chemotherapy, 2009, v. 53 n. 9, p. 3935-3941en_HK
dc.identifier.issn0066-4804en_HK
dc.identifier.urihttp://hdl.handle.net/10722/79018-
dc.description.abstractDAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing the virus receptor, sialic acid (Sia), from the adjacent glycan structures. DAS181 and its analogues have previously been shown to be potently active against multiple strains of seasonal and avian influenza virus strains in several experimental models, including cell lines, mice, and ferrets. Here we demonstrate that DAS181 treatment leads to desialylation of both α2-6-linked and α2-3-linked Sia in ex vivo human lung tissue culture and primary pneumocytes. DAS181 treatment also effectively protects human lung tissue and pneumocytes against the highly pathogenic avian influenza virus H5N1 (A/Vietnam/3046/2004). Two doses of DAS181 treatment given 12 h apart were sufficient to block H5N1 infection in the ex vivo lung tissue culture. These findings support the potential value of DAS181 as a broad-spectrum therapeutic agent against influenza viruses, especially H5N1. Copyright © 2009, American Society for Microbiology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology.en_HK
dc.relation.ispartofAntimicrobial Agents and Chemotherapyen_HK
dc.rightsAntimicrobial Agents and Chemotherapy. Copyright © American Society for Microbiology.en_HK
dc.rightsCopyright © American Society for Microbiology, [insert journal name, volume number, page numbers, and year]-
dc.subject.meshAntiviral Agents - pharmacology-
dc.subject.meshInfluenza A Virus, H5N1 Subtype - drug effects-
dc.subject.meshInfluenza, Human - prevention and control - virology-
dc.subject.meshLung - cytology - drug effects - virology-
dc.subject.meshRecombinant Fusion Proteins - pharmacology-
dc.titleDAS181 inhibits H5N1 influenza virus infection of human lung tissuesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0066-4804&volume=53&issue=9&spage=3935&epage=3941&date=2009&atitle=DAS181+inhibits+H5N1+influenza+virus+infection+of+human+lung+tissuesen_HK
dc.identifier.emailChan, RWY: reneewy@hku.hken_HK
dc.identifier.emailChan, MCW: mchan@hku.hken_HK
dc.identifier.emailMalik Peiris, JS: malik@hkucc.hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.authorityChan, RWY=rp01596en_HK
dc.identifier.authorityChan, MCW=rp00420en_HK
dc.identifier.authorityMalik Peiris, JS=rp00410en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/AAC.00389-09en_HK
dc.identifier.pmid19596886en_HK
dc.identifier.pmcidPMC2737896-
dc.identifier.scopuseid_2-s2.0-70349122523en_HK
dc.identifier.hkuros160048en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349122523&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume53en_HK
dc.identifier.issue9en_HK
dc.identifier.spage3935en_HK
dc.identifier.epage3941en_HK
dc.identifier.eissn1098-6596-
dc.identifier.isiWOS:000270014200043-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridChan, RWY=26661379100en_HK
dc.identifier.scopusauthoridChan, MCW=26654715500en_HK
dc.identifier.scopusauthoridWong, ACN=35749351000en_HK
dc.identifier.scopusauthoridKaramanska, R=24490944900en_HK
dc.identifier.scopusauthoridDell, A=7103412653en_HK
dc.identifier.scopusauthoridHaslam, SM=7005784726en_HK
dc.identifier.scopusauthoridSihoe, ADL=6603611976en_HK
dc.identifier.scopusauthoridChui, WH=7003524497en_HK
dc.identifier.scopusauthoridTrianaBaltzer, G=6504655978en_HK
dc.identifier.scopusauthoridLi, Q=35748971500en_HK
dc.identifier.scopusauthoridMalik Peiris, JS=7005486823en_HK
dc.identifier.scopusauthoridFang, F=7202929817en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK

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