Pharmaceutical Research

, Volume 27, Issue 2, pp 259–263 | Cite as

Bifunctional Polymeric Inhibitors of Human Influenza A Viruses

  • Jayanta Haldar
  • Luis Álvarez de Cienfuegos
  • Terrence M. Tumpey
  • Larisa V. Gubareva
  • Jianzhu ChenEmail author
  • Alexander M. KlibanovEmail author
Research Paper



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.


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.


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.


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.


drug-resistant mutant influenza virus polymeric antiviral agents sialic acid zanamivir 



This work was financially supported by NIH grant U01-AI074443. L.A.d.C. is grateful to Fundacion Ramon Areces of Spain for a postdoctoral fellowship.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jayanta Haldar
    • 1
  • Luis Álvarez de Cienfuegos
    • 1
  • Terrence M. Tumpey
    • 2
  • Larisa V. Gubareva
    • 2
  • Jianzhu Chen
    • 3
    Email author
  • Alexander M. Klibanov
    • 1
    • 4
    Email author
  1. 1.Department of ChemistryMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Centers for Disease Control and PreventionAtlantaUSA
  3. 3.Department of Biology and the David H. Koch Institute for Integrative Cancer ResearchMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA

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