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1000 Titel
  • Utilising animal models to evaluate oseltamivir efficacy against influenza A and B viruses with reduced in vitro susceptibility
1000 Autor/in
  1. Farrukee, Rubaiyea |
  2. Tai, Celeste |
  3. Oh, Ding Yuan |
  4. Anderson, Danielle |
  5. Gunalan, Vithiagaran |
  6. Hibberd, Martin |
  7. Lau, Gary Yuk-Fai |
  8. Barr, Ian G. |
  9. von Messling, Veronika |
  10. Maurer-Stroh, Sebastian |
  11. Hurt, Aeron |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-06-18
1000 Erschienen in
1000 Quellenangabe
  • 16(6):e1008592
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.ppat.1008592 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326275/ |
1000 Ergänzendes Material
  • https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008592#sec020 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the efficacy of OST against these viruses in vivo is not well understood. In this study, a ferret model was utilised to evaluate OST efficacy against circulating influenza A and B viruses with a range of in vitro generated 50% inhibitory concentrations (IC50) values for OST. OST efficacy against an A(H1N1)pdm09 and an A(H1N1)pdm09 virus with the H275Y substitution in neuraminidase was also tested in the macaque model. The results from this study showed that OST had a significant impact on virological parameters compared to placebo treatment of ferrets infected with wild-type influenza A viruses with normal IC50 values (~1 nM). However, this efficacy was lower against wild-type influenza B and other viruses with higher IC50 values. Differing pathogenicity of the viruses made evaluation of clinical parameters difficult, although some effect of OST in reducing clinical signs was observed with influenza A(H1N1) and A(H1N1)pdm09 (H275Y) viruses. Viral titres in macaques were too low to draw conclusive results. Analysis of the ferret data revealed a correlation between IC50 and OST efficacy in reducing viral shedding but highlighted that the current WHO guidelines/criteria for defining normal, reduced or highly reduced inhibition in influenza B viruses based on in vitro data are not well aligned with the low in vivo OST efficacy observed for both wild-type influenza B viruses and those with reduced OST susceptibility.
1000 Sacherschließung
lokal Macaque
lokal H1N1
lokal Ferrets
lokal Influenza
lokal Viral release
lokal Influenza viruses
lokal Influenza A virus
lokal Influenza B virus
gnd 4022090-4 Grippe
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-9023-246X|https://orcid.org/0000-0002-5148-8929|https://frl.publisso.de/adhoc/uri/ICAgT2gsIERpbmcgWXVhbiAgICAg|https://orcid.org/0000-0003-4791-5024|https://orcid.org/0000-0002-2020-9739|https://orcid.org/0000-0001-8587-1849|https://frl.publisso.de/adhoc/uri/ICAgTGF1LCBHYXJ5IFl1ay1GYWkgICAgIA==|https://frl.publisso.de/adhoc/uri/QmFyciwgSWFuIEcuICAgIA==|https://orcid.org/0000-0002-3972-8723|https://orcid.org/0000-0003-0813-9640|https://orcid.org/0000-0003-1826-4314
1000 Label
1000 Förderer
  1. Department of Health, Australian Government |
  2. National Health and Medical Research Council |
1000 Fördernummer
  1. -
  2. APP1055793
1000 Förderprogramm
  1. Melbourne WHO Collaborating Centre for Reference and Research on Influenza
  2. NHMRC-A*STAR grant
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Department of Health, Australian Government |
    1000 Förderprogramm Melbourne WHO Collaborating Centre for Reference and Research on Influenza
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer National Health and Medical Research Council |
    1000 Förderprogramm NHMRC-A*STAR grant
    1000 Fördernummer APP1055793
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6432453.rdf
1000 Erstellt am 2022-03-22T16:28:47.578+0100
1000 Erstellt von 323
1000 beschreibt frl:6432453
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Thu Apr 21 10:19:37 CEST 2022
1000 Objekt bearb. Thu Apr 21 10:19:23 CEST 2022
1000 Vgl. frl:6432453
1000 Oai Id
  1. oai:frl.publisso.de:frl:6432453 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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