Structural basis for oseltamivir resistanc of influenza viruses

PJ Collins, LF Haire, YP Lin, J Liu, Rupert James Martin Russell, PA Walker, SR Martin, RS Daniels, V Gregory, JJ Skehel, SJ Gamblin, AJ Hay

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)

Abstract

Oseltamivir, one of the two anti-neuraminidase drugs, is currently the most widely used drug against influenza. Resistance to the drug has occurred infrequently among different viruses in response to drug treatment, including A H5N1 viruses, but most notably has emerged among recently circulating A H1N1 viruses and has spread throughout the population in the absence of drug use. Crystal structures of enzyme-drug Complexes, together with enzymatic properties, of mutants of H5N1 neuraminidase have provided explanations for high level oseltamivir resistance due to the common H275Y mutation, with retention of zanamivir susceptibility, and intermediate level resistance due to the N295S mutation. Complementation of enhanced NA activity due to a D344N mutation by the H275Y mutation suggests an explanation for the recent emergence and predominance of oseltamivir-resistant influenza A H1N1 viruses. (C) 2009 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)6317-6323
Number of pages7
JournalVaccine
Volume27
DOIs
Publication statusPublished - 23 Oct 2009

Keywords

  • Influenza H5N1
  • Oseltamivir resistance
  • H275Y mutation
  • NEURAMINIDASE INHIBITORS
  • AVIAN INFLUENZA
  • IN-VITRO
  • DESIGN
  • REPLICATION
  • SEASON
  • VIVO
  • FLU

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