Pharmaceutical Research

, Volume 27, Issue 2, pp 259–263

Bifunctional Polymeric Inhibitors of Human Influenza A Viruses


  • Jayanta Haldar
    • Department of ChemistryMassachusetts Institute of Technology
  • Luis Álvarez de Cienfuegos
    • Department of ChemistryMassachusetts Institute of Technology
  • Terrence M. Tumpey
    • Centers for Disease Control and Prevention
  • Larisa V. Gubareva
    • Centers for Disease Control and Prevention
    • Department of Biology and the David H. Koch Institute for Integrative Cancer ResearchMassachusetts Institute of Technology
    • Department of ChemistryMassachusetts Institute of Technology
    • Department of Biological EngineeringMassachusetts Institute of Technology
Research Paper

DOI: 10.1007/s11095-009-0013-1

Cite this article as:
Haldar, J., Álvarez de Cienfuegos, L., Tumpey, T.M. et al. Pharm Res (2010) 27: 259. doi:10.1007/s11095-009-0013-1



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

Copyright information

© Springer Science+Business Media, LLC 2009