Influenza Virus Susceptibility and Resistance to Oseltamivir

@article{Aoki2007InfluenzaVS,
  title={Influenza Virus Susceptibility and Resistance to Oseltamivir},
  author={Fred Y. Aoki and Guy Boivin and Noel Allan Roberts},
  journal={Antiviral Therapy},
  year={2007},
  volume={12},
  pages={603 - 616}
}
Oseltamivir phosphate is a prodrug of oseltamivir carboxylate, a highly specific inhibitor of influenza virus neuraminidases. Given that oseltamivir carboxylate binds to highly conserved, essential amino acids in the catalytic site of the enzyme, and that the activity of neuraminidase is critical for virus release from infected cells and subsequent virus spread, the drug was expected to have a low propensity to select for viable resistant mutants. Indeed, viruses with neuraminidase (and… 

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References

SHOWING 1-10 OF 86 REFERENCES

Susceptibilities of Antiviral-Resistant Influenza Viruses to Novel Neuraminidase Inhibitors

TLDR
It is indicated that different patterns of susceptibility and cross-resistance between NA inhibitors may prove important if antiviral resistance to zanamivir and oseltamivIR were to emerge.

Resistant influenza A viruses in children treated with oseltamivir: descriptive study

Neuraminidase Sequence Analysis and Susceptibilities of Influenza Virus Clinical Isolates to Zanamivir and Oseltamivir

TLDR
The baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors are established and there was no evidence of naturally occurring resistance to either drug in any of the isolates.

Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors.

TLDR
In this population, influenza B viruses with reduced sensitivity to neuraminidase inhibitors do not arise as frequently as resistant influenza A viruses, however, they appear to be transmitted within communities and families, requiring continued close monitoring.

Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus.

TLDR
The data indicate that the current methods for monitoring resistant mutants are potentially flawed because no tissue culture system adequately reflects the receptor specificity of human respiratory tract epithelium.

Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir.

TLDR
Hemagglutinin affinity for receptors is an essential feature of influenza virus susceptibility to NA inhibitors, both in cell culture and in humans.

Treatment of influenza with neuraminidase inhibitors: virological implications.

  • N. Roberts
  • Biology, Medicine
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 2001
Evaluation of the emergence of influenza virus resistance to neuraminidase inhibitors (NAIs) is now demanded following experience with amantadinamines. Preliminary data have indicated that

USE OF THE SELECTIVE ORAL NEURAMINIDASE INHIBITOR OSELTAMIVIR TO PREVENT INFLUENZA

TLDR
Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza.
...