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dc.contributor.authorHaldar, Jayanta
dc.contributor.authorAlvarez de Cienfuegos, Luis
dc.contributor.authorTumpey, Terrence M.
dc.contributor.authorGubareva, Larisa V.
dc.contributor.authorChen, Jianzhu
dc.contributor.authorKlibanov, Alexander M.
dc.date.accessioned2012-09-20T19:24:03Z
dc.date.available2012-09-20T19:24:03Z
dc.date.issued2010-02
dc.date.submitted2009-09
dc.identifier.issn0724-8741
dc.identifier.issn1573-904X
dc.identifier.urihttp://hdl.handle.net/1721.1/73085
dc.description.abstractPurpose: New antiviral agents were prepared by attaching derivatives of sialic acid (1) and of the drug zanamivir (2) to poly(isobutylene-alt-maleic anhydride) (poly-(1 + 2)) or by mixing poly-1 and poly-2, followed by assaying them against wild-type and drug-resistant influenza A Wuhan viruses. Methods: Individually or together, 1 and 2 were covalently bonded to the polymer. The antiviral potencies of the resultant poly-1, poly-2, poly-(1 + 2), and poly-1 + poly-2, as well as 1 and 2, were assessed using plaque reduction assay. Results: Attaching 1 to the polymer improved at best millimolar IC50 values over three orders of magnitude. While 2 exhibited micromolar IC50 values, poly-2 was >100-fold even more potent. The IC50 of poly-(1 + 2) against the wild-type strain was >300-fold and ∼17-fold better than of poly-1 and poly-2, respectively. In contrast, the potency of poly-(1 + 2) vs. poly-2 against the mutant strain merely doubled. The mixture of poly-1 + poly-2 inhibited both viral strains similarly to poly-2. Conclusions: The bifunctional poly-(1 + 2) acts synergistically against the wild-type influenza virus, but not against its drug-resistant mutant, as compared to a physical mixture of the monofunctional poly-1 and poly-2.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant U01-AI074443)en_US
dc.description.sponsorshipFundación Ramón Areces (postdoctoral fellowship)en_US
dc.language.isoen_US
dc.publisherSpringer Science + Business Media B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1007/s11095-009-0013-1en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourcePMCen_US
dc.titleBifunctional Polymeric Inhibitors of Human Influenza A Virusesen_US
dc.typeArticleen_US
dc.identifier.citationHaldar, Jayanta et al. “Bifunctional Polymeric Inhibitors of Human Influenza A Viruses.” Pharmaceutical Research 27.2 (2009): 259–263. Web.en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorKlibanov, Alexander M.
dc.contributor.mitauthorAlvarez de Cienfuegos, Luis
dc.contributor.mitauthorChen, Jianzhu
dc.relation.journalPharmaceutical Researchen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHaldar, Jayanta; Álvarez de Cienfuegos, Luis; Tumpey, Terrence M.; Gubareva, Larisa V.; Chen, Jianzhu; Klibanov, Alexander M.en
dc.identifier.orcidhttps://orcid.org/0000-0003-3830-714X
dc.identifier.orcidhttps://orcid.org/0000-0002-5687-6154
mit.licenseOPEN_ACCESS_POLICYen_US


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