Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus.
Method: Recombinant baculoviruses were generated to express the wild-type, H274Y, H274Y and I222R mutants of NA originating from influenza N1 neuraminidase (NIBRG14 (H5N1)).
Method: The NA structure with I222R and H274Y dual-point mutations was derived using a homology-modeling server.
Method: The assay was conducted in 96-well plates containing active wild-type, H274Y, H274Y and I222R mutants of NA and 100 muM fluorogenic substrate per well in reaction buffer.
Method: The oseltamivir-resistant NA contains a PMID: 29107426
2017
European journal of medicinal chemistry
Abstract: Moreover, 11b showed moderate inhibitions against mutant neuraminidases from H5N1-H274Y and H1N1-H274Y with IC50 values of 2075 nM and 1382 nM, which were inferior to those of oseltamivir carboxylate (6095 nM and 4071 nM).
A Novel Potent and Highly Specific Inhibitor against Influenza Viral N1-N9 Neuraminidases: Insight into Neuraminidase-Inhibitor Interactions.
PMID: 27095056
2016
Journal of medicinal chemistry
Abstract: Like zanamivir, it is highly effective against N1-N9 avian and N1-N2 human viNAs, including H274Y oseltamivir-resistant N1 viNA, due to its C-6 portion still being anchored in the active site, different from the disruption of oseltamivir's C-6 anchoring by H274Y mutation.
Residue-based design of small molecule inhibitor for H1N1, H5N1 and H7N1 mutants.
Abstract: Our in silico findings suggest that saussureamine C can inhibit H274Y and N294S mutants, and that diiodotyrosine can also inhibit N294S mutants.
Abstract: Point mutations H274Y and N294S can lead to resistance of influenza virus strains to some drug molecules.
Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus.
PMID: 26703840
2016
Journal of chemical information and modeling
Abstract: However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear.
Abstract: Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern.
Abstract: It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274.
Abstract: Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y
Detection of reassortant avian influenza A (H11N9) virus in environmental samples from live poultry markets in China.
PMID: 27268229
2016
Infectious diseases of poverty
Table: H274Y
Sensitive Detection and Simultaneous Discrimination of Influenza A and B Viruses in Nasopharyngeal Swabs in a Single Assay Using Next-Generation Sequencing-Based Diagnostics.
Introduction: Current methods that evaluate antiviral resistance require two independent tests for the S31N substitutions conferring amantadine-resistance and the H274Y substitution conferring oseltamivir-resistance.
Risk of resistant avian influenza A virus in wild waterfowl as a result of environmental release of oseltamivir.
Abstract: In an A(H1N1)/H274Y virus, the OC resistance mutation persisted without selective drug pressure, demonstrating the potential of an IAV with a permissive genetic background to acquire and maintain OC resistance, potentially allowing circulation of the resistant variant among wild birds.
Introduction: However, since 2010/2011, an increasing number of community cases with OC-resistant A(H1N1)/pdm09 viruses have been reported without previous oseltamivir exposure; in nearly all instances the resistance has been conferred by the H274Y substitution in NA.
Introduction: In IAVs containing N1 NA proteins the most common resistance-related change seen in vivo is the framework substitution H274Y (N2 numbering, used hereafter), whereas in N2-containing viruses the framework E119V
Platform for determining the inhibition profile of neuraminidase inhibitors in an influenza virus N1 background.
PMID: 27659246
2016
Journal of virological methods
Abstract: Employing reverse genetics, a set of influenza virus variants containing an amino acid substitution associated with oseltamivir resistance in N1 isolates (H274Y, N294S, Y155H or Q136L) was generated.
Abstract: For 5-amidino and 5-guanidino analogs of oseltamivir a significantly stronger inhibition of virus variants carrying a NA-H274Y was confirmed, and additionally shown for NA-N294S and NA-Y155H substitutions as compared to the parent compound.
Abstract: Novel NAIs should in particular be also effective against seasonal and/or pandemic N1 that carry a H274Y
Human Monoclonal Antibody 81.39a Effectively Neutralizes Emerging Influenza A Viruses of Group 1 and 2 Hemagglutinins.
IV mutation literature information.
PMID: 
2017
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