Resistance Development to Influenza Virus Sialidase Inhibitors

  • Marie-Anne Rameix-Welti
  • Sandie Munier
  • Nadia Naffakh
Part of the Milestones in Drug Therapy book series (MDT)


The emergence of influenza viruses resistant to sialidase (neuraminidase, NA) inhibitors (NAIs) upon treatment is observed at low frequencies in adult immunocompetent patients, and does not impact significantly the evolution of influenza syndrome. In contrast, the development of resistance to NAIs is of clinical concern in immunocompromised patients and in patients with zoonotic influenza. Resistance mutations affect residues that are close to or belong to the catalytic site of the enzyme. Structural data provide clues about the subtype specificity of resistance mutations and the absence of cross-resistance to oseltamivir and zanamivir. Experimental data pointed to a negative impact of resistance mutations on viral fitness and transmissibility. However, H1N1 viruses naturally resistant to oseltamivir did emerge and spread in 2007–2008, which compromises the clinical effectiveness of the drug. This unexpected event stresses the need for a close surveillance of the impact of genetic drift on the susceptibility of influenza viruses to NAIs and for the further development of novel anti-influenza drugs.


Influenza Virus Sialic Acid Resistance Mutation H1N1 Virus Resistant Virus 



We are very grateful to Jeffrey Dyason and Mark von Itzstein for providing Fig. 1.


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Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Marie-Anne Rameix-Welti
    • 1
    • 2
    • 3
    • 4
  • Sandie Munier
    • 1
    • 2
    • 3
  • Nadia Naffakh
    • 1
    • 2
    • 3
  1. 1.Unité de Génétique Moléculaire des Virus à ARN, Département de VirologieInstitut PasteurParisFrance
  2. 2.CNRS URA3015ParisFrance
  3. 3.Sorbonne Paris Cité, Unité de Génétique Moléculaire des Virus à ARNUniversité Paris-DiderotParisFrance
  4. 4.Université Versailles Saint-Quentin-en-YvelinesGuyancourtFrance

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