Journal
ANTIVIRAL RESEARCH
Volume 114, Issue -, Pages 62-66Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2014.12.004
Keywords
Influenza; Laninamivir; Resistance; Enzyme kinetics
Categories
Funding
- CSIRO
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The neuraminidase (NA) inhibitors oseltamivir and zanamivir are administered twice daily for 5 days for treatment of influenza. Laninamivir is a 7-methoxy derivative of zanamivir, but a single dose is effective when taken as the laninamivir octanoate prodrug. We show here in IC50 kinetics assays and a solid phase reactivation assay that compared to zanamivir laninamivir also demonstrates slow binding to but slower dissociation from multiple wild type NAs. A D197E mutation in an influenza B and an E119G in an N9 neuraminidase which confer 15- and 150-fold resistance to laninamivir result in faster binding and dissociation. Despite similar IC(50)s our assays demonstrate more rapid dissociation of laninamivir from clade 1 compared to 2 H5N1 NAs. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved.
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