Attaching zanamivir to a polymer markedly enhances its activity against drug-resistant strains of influenza a virus
✍ Scribed by Alisha K. Weight; Jayanta Haldar; Luis Álvarez de Cienfuegos; Larisa V. Gubareva; Terrence M. Tumpey; Jianzhu Chen; Alexander M. Klibanov
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 193 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
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.