ArticleThe Journal of infectious diseases2014
A novel I221L substitution in neuraminidase confers high-level resistance to oseltamivir in influenza B viruses.
Article in The Journal of infectious diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 29 citations in OpenAlex.
- Divergent pathogenic mechanisms of influenza A and influenza B viruses.Archives of microbiology · 2026Review
- Multi-target computational pipeline for discovery of pan-influenza neuraminidase inhibitors.Frontiers in pharmacology · 2026Article
- Functionality of the putative surface glycoproteins of the Wuhan spiny eel influenza virus.Nature communications · 2021Article
- Article
- Is oseltamivir suitable for fighting against COVID-19: In silico assessment, in vitro and retrospective study.Bioorganic chemistry · 2020Article
- Influenza B viruses from different genetic backgrounds are variably impaired by neuraminidase inhibitor resistance-associated substitutions.Antiviral research · 2020Article
- Detection and Characterization of Influenza B Virus With Reduced Neuraminidase Susceptibility in a Stem Cell Transplant Recipient.Open forum infectious diseases · 2019Article
- Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
- Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2012-2013.Antiviral research · 2014Article
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
unlabelledInfluenza B viruses with a novel I221L substitution in neuraminidase (NA) conferring high-level resistance to oseltamivir were isolated from an immunocompromised patient after prolonged oseltamivir treatment.
methodsEnzymatic characterization of the NAs (Km, Ki) and the in vitro fitness of viruses carrying wild-type or mutated (I221L) NA genes were evaluated. Proportions of wild-type and mutated NA genes were directly quantified in the patient samples. Structural characterizations by X-ray crystallography of a wild-type and I221L variant NA were performed.
resultsThe Km and Ki revealed that the I221L variant NA had approximately 84 and 51 times lower affinity for oseltamivir carboxylate and zanamivir, respectively, compared with wild-type NA. Viruses with a wild-type or I221L variant NA had similar growth kinetics in Madin-Darby canine kidney (MDCK) cells, and 5 passages in MDCK cells revealed no reversion of the I221L substitution. The crystal structure of the I221L NA and oseltamivir complex showed that the leucine side chain protrudes into the hydrophobic pocket of the active site that accommodates the pentyloxy substituent of oseltamivir.
conclusionsEnzyme kinetic and NA structural analyses provide an explanation for the high level of resistance to oseltamivir while retaining good fitness of viruses carrying I221L variant NA.
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