ArticleViruses2018
Kinetic, Thermodynamic, and Structural Analysis of Drug Resistance Mutations in Neuraminidase from the 2009 Pandemic Influenza Virus.
Article in Viruses, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2026Article
- Detection and characterization of antiviral-resistant viruses during the influenza season of 2024-25.Microbiology spectrum · 2026Article
- Multi-target computational pipeline for discovery of pan-influenza neuraminidase inhibitors.Frontiers in pharmacology · 2026Article
- Neuraminidase reassortment and oseltamivir resistance in clade 2.3.4.4b A(H5N1) viruses circulating among Canadian poultry, 2024.Emerging microbes & infections · 2025Article
- Expansion of influenza A(H1N1)pdm09 NA:S247N viruses with reduced susceptibility to oseltamivir, Catalonia, Spain, and in Europe, July to October 2025.Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2025Article
- Genomic signatures and host adaptation of H5N1 clade 2.3.4.4b: A call for global surveillance and multi-target antiviral strategies.Current research in microbial sciences · 2025Article
- 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
- A Novel Prodrug Strategy Based on Reversibly Degradable Guanidine Imides for High Oral Bioavailability and Prolonged Pharmacokinetics of Broad-Spectrum Anti-influenza Agents.ACS central science · 2024Article
- Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases.Viruses · 2024Article
- MedChemExpress compounds prevent neuraminidase N1RSC advances · 2024Article
- An orally active entry inhibitor of influenza A viruses protects mice and synergizes with oseltamivir and baloxavir marboxil.Science advances · 2024Article
- Article
- The importance of residue-level filtering and the Top2018 best-parts dataset of high-quality protein residues.Protein science : a publication of the Protein Society · 2022Article
- Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir.Microorganisms · 2021Article
- Structural and Thermodynamic Analysis of the Resistance Development to Pimodivir (VX-787), the Clinical Inhibitor of Cap Binding to PB2 Subunit of Influenza A Polymerase.Molecules (Basel, Switzerland) · 2021Article
- Coding-Complete Genome Sequences of Six Influenza Type A Strains Circulating in Lithuania in the 2009-2010 Epidemic Season.Microbiology resource announcements · 2021Article
- N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.Journal of virology · 2020Article
- Combining structure and genomics to understand antimicrobial resistance.Computational and structural biotechnology journal · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuraminidase is the main target for current influenza drugs. Reduced susceptibility to oseltamivir, the most widely prescribed neuraminidase inhibitor, has been repeatedly reported. The resistance substitutions I223V and S247N, alone or in combination with the major oseltamivir-resistance mutation H275Y, have been observed in 2009 pandemic H1N1 viruses. We overexpressed and purified the ectodomain of wild-type neuraminidase from the A/California/07/2009 (H1N1) influenza virus, as well as variants containing H275Y, I223V, and S247N single mutations and H275Y/I223V and H275Y/S247N double mutations. We performed enzymological and thermodynamic analyses and structurally examined the resistance mechanism. Our results reveal that the I223V or S247N substitution alone confers only a moderate reduction in oseltamivir affinity. In contrast, the major oseltamivir resistance mutation H275Y causes a significant decrease in the enzyme’s ability to bind this drug. Combination of H275Y with an I223V or S247N mutation results in extreme impairment of oseltamivir’s inhibition potency. Our structural analyses revealed that the H275Y substitution has a major effect on the oseltamivir binding pose within the active site while the influence of other studied mutations is much less prominent. Our crystal structures also helped explain the augmenting effect on resistance of combining H275Y with both substitutions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.