Attaching zanamivir to a polymer markedly enhances its activity against drug-resistant strains of influenza a virus

• Main Authors: Weight, Alisha Kessel (Contributor), Haldar, Jayanta (Contributor), Cienfuegos, Luis Álvarez de (Contributor), Gubareva, Larisa V. (Author), Tumpey, Terrence M. (Author), Chen, Jianzhu (Contributor), Klibanov, Alexander M. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: Wiley Blackwell (John Wiley & Sons), 2012-08-01T18:26:55Z.
• Subjects: Article
• Online Access: Get fulltext

Effects of the commercial drug zanamivir (Relenza™) covalently attached to poly-l-glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti-influenza potency compared with the zanamivir parent against human and avian viral strains, including both wild-type and drug-resistant mutants, and (ii) superior neuraminidase (NA) inhibition constants, especially for the mutants. These findings provide a basis for exploring polymer-attached inhibitors as more efficacious therapeutics, particularly against drug-resistant influenza strains.
National Institutes of Health (U.S.) (Grant Number U01-AI074443)
Fundación Ramón Areces. Postdoctoral Fellowship