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Neuraminidase mutations conferring resistance to laninamivir lead to faster drug binding and dissociation.
- Source :
-
Antiviral research [Antiviral Res] 2015 Feb; Vol. 114, pp. 62-6. Date of Electronic Publication: 2014 Dec 09. - Publication Year :
- 2015
-
Abstract
- The neuraminidase (NA) inhibitors oseltamivir and zanamivir are administered twice daily for 5days 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 IC50s our assays demonstrate more rapid dissociation of laninamivir from clade 1 compared to 2 H5N1 NAs.<br /> (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antiviral Agents pharmacology
Dogs
Drug Resistance, Viral genetics
Guanidines
Influenza A Virus, H5N1 Subtype drug effects
Influenza A Virus, H5N1 Subtype enzymology
Influenza A virus drug effects
Influenza A virus enzymology
Influenza B virus drug effects
Influenza B virus enzymology
Inhibitory Concentration 50
Madin Darby Canine Kidney Cells
Mutation
Oseltamivir metabolism
Oseltamivir pharmacology
Pyrans
Sialic Acids
Viral Proteins genetics
Viral Proteins metabolism
Zanamivir metabolism
Zanamivir pharmacology
Antiviral Agents metabolism
Influenza A Virus, H5N1 Subtype genetics
Influenza A virus genetics
Influenza B virus genetics
Neuraminidase genetics
Neuraminidase metabolism
Zanamivir analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 114
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 25499124
- Full Text :
- https://doi.org/10.1016/j.antiviral.2014.12.004