Neuraminidase mutations conferring resistance to laninamivir lead to faster drug binding and dissociation.
Antiviral Res
; 114: 62-6, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25499124
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Vírus da Influenza A
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Vírus da Influenza B
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Virus da Influenza A Subtipo H5N1
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Zanamivir
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Neuraminidase
Limite:
Animals
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2015
Tipo de documento:
Article