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Article: Novel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein

TitleNovel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2009, v. 4 n. 11 How to Cite?
AbstractBackground: The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase)™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses. Methods and Findings: The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus. Conclusions: The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV.
Persistent Identifierhttp://hdl.handle.net/10722/57598
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTrianaBaltzer, GBen_HK
dc.contributor.authorGubareva, LVen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorPearce, MBen_HK
dc.contributor.authorMishin, VPen_HK
dc.contributor.authorBelser, JAen_HK
dc.contributor.authorChen, LMen_HK
dc.contributor.authorChan, RWYen_HK
dc.contributor.authorChan, MCWen_HK
dc.contributor.authorHedlund, Men_HK
dc.contributor.authorLarson, JLen_HK
dc.contributor.authorMoss, RBen_HK
dc.contributor.authorKatz, JMen_HK
dc.contributor.authorTumpey, TMen_HK
dc.contributor.authorFang, Fen_HK
dc.date.accessioned2010-04-21T03:29:26Z-
dc.date.available2010-04-21T03:29:26Z-
dc.date.issued2009en_HK
dc.identifier.citationPlos One, 2009, v. 4 n. 11en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57598-
dc.description.abstractBackground: The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase)™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses. Methods and Findings: The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus. Conclusions: The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV.en_HK
dc.language.isoengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsPLoS ONE. Copyright © Public Library of Science.en_HK
dc.subject.meshAntiviral Agents - pharmacology-
dc.subject.meshBronchi - metabolism-
dc.subject.meshInfluenza A Virus, H1N1 Subtype - metabolism-
dc.subject.meshNeuraminidase - chemistry-
dc.subject.meshRecombinant Fusion Proteins - chemistry - pharmacology-
dc.titleNovel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion proteinen_HK
dc.typeArticleen_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailChan, RWY: reneewy@hku.hken_HK
dc.identifier.emailChan, MCW: mchan@hku.hken_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityChan, RWY=rp01596en_HK
dc.identifier.authorityChan, MCW=rp00420en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1371/journal.pone.0007788en_HK
dc.identifier.pmid19893747-
dc.identifier.pmcidPMC2770640en_HK
dc.identifier.scopuseid_2-s2.0-70450175741en_HK
dc.identifier.hkuros168262-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70450175741&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue11en_HK
dc.identifier.isiWOS:000271478000013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTrianaBaltzer, GB=6504655978en_HK
dc.identifier.scopusauthoridGubareva, LV=7004253433en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridPearce, MB=35068454100en_HK
dc.identifier.scopusauthoridMishin, VP=55397752500en_HK
dc.identifier.scopusauthoridBelser, JA=12239548700en_HK
dc.identifier.scopusauthoridChen, LM=7409436729en_HK
dc.identifier.scopusauthoridChan, RWY=26661379100en_HK
dc.identifier.scopusauthoridChan, MCW=26654715500en_HK
dc.identifier.scopusauthoridHedlund, M=36905822100en_HK
dc.identifier.scopusauthoridLarson, JL=7202866566en_HK
dc.identifier.scopusauthoridMoss, RB=7402545144en_HK
dc.identifier.scopusauthoridKatz, JM=7403970287en_HK
dc.identifier.scopusauthoridTumpey, TM=6701520653en_HK
dc.identifier.scopusauthoridFang, F=7202929817en_HK

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