ArticleThe Journal of infectious diseases2015
E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient.
Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 74 citations in OpenAlex.
- Lessons from resistance analysis in clinical trials of IV zanamivir.Virus research · 2023Trial
- In vitro efficacy of anti-influenza active compounds against clinical isolates with high growth capability.Archives of virology · 2026Article
- A scoping review of influenza RdRp-targeting inhibitors: mechanisms, clinical translation, and emerging challenges.Frontiers in microbiology · 2026Review
- Pathogenesis of MRSA-influenza co-infection: implications for ECMO therapeutic strategies - a mini-review.Frontiers in immunology · 2026Review
- Influenza and Aging: Clinical Manifestations, Complications, and Treatment Approaches in Older Adults.Drugs & aging · 2025Review
- Molecular dynamics study on the effect of the N1 neuraminidase double mutant G147R/H274Y on oseltamivir sensitivity.RSC advances · 2024Article
- Influenza neuraminidase mutations and resistance to neuraminidase inhibitors.Emerging microbes & infections · 2024Review
- Drug resistance and possible therapeutic options against influenza A virus infection over past years.Archives of microbiology · 2024Review
- Resistance profiles for the investigational neuraminidase inhibitor AV5080 in influenza A and B viruses.Antiviral research · 2023Article
- Phylogenetic analysis of HA and NA genes of influenza A viruses in immunosuppressed inpatients in Beijing during the 2018-2020 influenza seasons.Virology journal · 2023Article
- Influenza antivirals and their role in pandemic preparedness.Antiviral research · 2023Review
- Structural and inhibitor sensitivity analysis of influenza B-like viral neuraminidases derived from Asiatic toad and spiny eel.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Influenza A virus polymerase acidic protein E23G/K substitutions weaken key baloxavir drug-binding contacts with minimal impact on replication and transmission.PLoS pathogens · 2022Article
- Antivirals Targeting the Neuraminidase.Cold Spring Harbor perspectives in medicine · 2022Review
- Influenza A Virus Neuraminidase Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Broad-spectrum Respiratory Virus Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir.Microorganisms · 2021Article
- Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance.Viruses · 2021Review
- The Entry Blocker Peptide Produced inFrontiers in plant science · 2021Article
- Article
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14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAn influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy.
methodsRecombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies.
resultsWe identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT.
conclusionsThe actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategies.
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