Virtual screening for oseltamivir-resistant a (H5N1) influenza neuraminidase from traditional Chinese medicine database: a combined molecular docking with molecular dynamics approach.
Abstract: Most importantly, H274Y mutation in neuraminidase exhibits high levels of resistance to oseltamivir.
Introduction: In particular H274Y, the principal mutation isolated in association with oseltamivir treatment that is specific to the N1 group (Yen et al.) and that has recently been shown to be present in substantial numbers of H5N1 viruses isolated from humans (Uyeki).
Method: The native and mutant (H274Y) type coordinates of NA were taken from the Brookhaven Protein Data Bank (Berman et al.).
Result: Despite the H274Y mutation in the structure of NA, neoglucobrassicin were retained the interaction with the residues R-371 and R-152 as like the wild type NA.
Result: It is evide
Occurrence and characterization of oseltamivir-resistant influenza virus in children between 2007-2008 and 2008-2009 seasons.
Method: For the genotypic analysis, mutations of amino acid regions related to drug resistance (E119V, R152K, H274Y, R292K, and N294S) were examined, via sequence analysis of NA gene.
Result: NA gene analysis was conducted on influenza viruses isolated from 51 patients (group A, 29 patients; group B, 22 patients) during the first study period in order to examine the drug resistance-related mutation of NA inhibitor (E119V, R152K, H274Y, R292K, N294S).
Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan.
Abstract: Among influenza A(H1N1)pdm09 viruses, the prevalence of H274Y viruses increased from 0% in the 2009-2010 season to 3% in the 2010-2011 season.
Abstract: For paired samples that were collected before and after drug treatment, three (3/11; 27.3%) H274Y viruses were identified among A(H1N1)pdm09 viruses after oseltamivir treatment but no outliers were found in the laninamivir-treatment group (n=3).
Abstract: These H274Y viruses were resistant to oseltamivir and peramivir with 200-300 fold increase in IC50 values but remained sensitive to zanamivir and laninamivir.
Functional and structural analysis of influenza virus neuraminidase N3 offers further insight into the mechanisms of oseltamivir resistance.
Abstract: Furthermore, we found that members of NA serotype N3 also possess Y252, raising the key question as to whether or not H274Y resistance may also be possible for some group 2 NAs.
Abstract: Here, we demonstrate that the H274Y substitution results in mild oseltamivir resistance for N3.
Abstract: However, H274Y has only been reported in N1 subtypes, which indicates that there must be additional key residues that determine H274Y resistance.
Abstract: Previous structural studies suggest that the group specific 252 residue (Y252 in group 1 and T252 in group 2) might be a key factor underlying H274Y resistance.
Abstract: The influenza virus neuraminidase PMID: 23860768
2013
mBio
Discussion: Surveillance studies suggest that the emergence of NA mutations conferring resistance to NA inhibitors has reportedly been low, with the exception of the naturally emergent H274Y NA mutation in H1N1 seasonal influenza viruses during the influenza season of 2007 to 2008.
Resistance mutation R292K is induced in influenza A(H6N2) virus by exposure of infected mallards to low levels of oseltamivir.
Abstract: We previously demonstrated that an influenza A(H1N1) virus
Discussion: It is possible that the additional mutations D113N or D141N in NA and/or E216K in HA might have influenced such an adaptation, like permissive mutations have been demonstrated in N1 virus that can compensate for the resistance mutation H274Y.
Discussion: We do however argue that there are reasons to take our results into environmental account as the threshold for resistance development could lie anywhere between 1.2 and 12 microg/L and as seen in our previous experiment with an A(H1N1) virus the resistance mutation (H274Y) was detected at 1 microg/L in only two samples; a similar resistance development could have been missed in the present, shorter experiment.
Characterization of two distinct neuraminidases from avian-origin human-infecting H7N9 influenza viruses.
Discussion: This is at a level much higher than even the prevalent H274Y oseltamivir-resistant substitution found in N1 viruses, which results in up to 1 200-fold resistance.
Generation and Characterization of Recombinant Influenza A(H1N1) Viruses Resistant to Neuraminidase Inhibitors.
PMID: 24524021
2013
Osong public health and research perspectives
Introduction: Other NA mutations (N2 numbering: E119G, H274Y, R292K, and N295S) that have been reported to confer resistance to NAIs were each introduced into recombinant A/Vietnam/1203/04(H5N1) influenza virus.
Synergistic combinations of favipiravir and oseltamivir against wild-type pandemic and oseltamivir-resistant influenza A virus infections in mice.
Discussion: In this report we used a wild-type (oseltamivirsensitive) pandemic H1N1 and oseltamivir-resistant H274Y seasonal H1N1 virus infections in mice for evaluating drug combination efficacy.
Antiviral effects of Psidium guajava Linn. (guava) tea on the growth of clinical isolated H1N1 viruses: its role in viral hemagglutination and neuraminidase inhibition.
Abstract: In contrast to both teas, oseltamivir carboxylate (OC) demonstrated high potency against the growth of A/Narita/1/09 (IC(50) of 3.83nM) and A/Yamaguchi/20/06 (IC(50) of 11.57nM) but not against that of A/Kitakyushu/10/06 bearing a His274-to-Tyr substitution (IC(50) of 15.97muM).
IV mutation literature information.
PMID: 
2013
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