Result: Six mutations are associated with the acquisition of resistance to neuramindase inhibitors, namely E119V, R152K, D198N, H274Y, R292K and N294S.
"Design, synthesis and biological evaluation of ""Multi-Site""-binding influenza virus neuraminidase inhibitors."
PMID: 31176096
2019
European journal of medicinal chemistry
Abstract: Among the synthesized compounds, compound 15e, the most potent N1-selective inhibitor targeting 150-cavity, showed 1.5 and 1.8 times greater activity than oseltamivir carboxylate (OSC) against N1 (H5N1) and N1 (H5N1-H274Y).
Abstract: Molecular docking studies provided insights into the high potency of 15e against N1 and N1-H274Y mutant NA.
Highly pathogenic avian influenza H7N9 viruses with reduced susceptibility to neuraminidase inhibitors showed comparable replication capacity to their sensitive counterparts.
Abstract: CONCLUSIONS: All 4 amino acid substitutions (R292 K, E119V, A246T or H274Y) in NA reduced the susceptibility of HPAI H7N9 to NAIs.
Abstract: RESULTS: Four potential NAI resistance sites, R292 K, E119V, A246T or H274Y, were screened.
Conclusion: <
Introduction: The research demonstrated that R292K and H274Y conferred a high increase in oseltamivir IC50, and E119D conferred the highest IC50 to zanamivir reported.
The evolution and characterization of influenza A(H7N9) virus under the selective pressure of peramivir.
Abstract: The NA-H274Y variant showed decreased replicative fitness at the early stage of infection accompanied with impaired NA function.
Abstract: Two important amino acid substitutions were identified in NA, I222T and H274Y, which caused reduced susceptibilities to oseltamivir or both oseltamivir and peramivir as confirmed by enzyme- and cell-based assays.
Molecular genetic characteristics of influenza A virus clinically isolated during 2011-2016 influenza seasons in Korea.
PMID: 29489060
2018
Influenza and other respiratory viruses
Discussion: However, other antidrug mutations, H274Y (N2 numbering) and I119V, were not confirmed.
Discussion: Previous studies have shown that the single I222V/M substitution in the NA protein is associated with marginal levels of resistance to oseltamivir, while synergistically increased drug resistance was associated with E119V and H274Y substitutions.15, 16, 19, 22, 23, 24, 25, 26 The S31N substitution in the M2 protein was frequently detected in the more recent viral sequences and reference sequences.27 In addition, V51I and I39M substitutions were identified in the 2011-2012 and 2014-2015 fatal case sequences.
Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.
Result: Next, one of the NA inhibitor-resistant mutations, NA/H274Y, was introduced in A/H1N1 and the susceptibility to BXA was determined.
Result: Whilst NA/H274Y results in a more than 200-fold reduction in susceptibility to oseltamivir acid, BXA showed potent activity against these viruses.
Table: H274Y
Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection.
PMID: 29688498
2018
The Journal of infectious diseases
Result: Among 10 other amino acids related to NAI resistance, only the H274Y mutation was detected in 1 sample from case 7; however, this resistant genotype reverted to the WT genotype 6 days later (Table 2).
Result: Sustained dual R292K and H274Y mutations were not detected in any of the samples.
Result: We conducted nucleotide polymorphism analysis of the sites related to NAI resistance in the NA segment, including R118K, E119V, D151E, R152K, I222V, R224K, H274Y,
Table: H274Y
Design and synthesis of constrained bicyclic molecules as candidate inhibitors of influenza A neuraminidase.
Abstract: This allowed the efficient preparation of a small library of new bicyclic ligands that were characterized by enzyme inhibition assays against influenza A neuraminidases N1, its H274Y mutant, and N2.
Introduction: It is now well known that the 3-pentyl ether side chain of oseltamivir is a major cause for resistance: neuraminidases must undergo a significant rearrangement to form a pocket for oseltamivir binding and this movement can be affected by mutations, such as H274Y.
Method: A/Chicken/HongKong/G9/1997 H9N2 and A/Anhui/1/2005 H5N1 (wild-type and H274Y mutation) were purchased from SinoBiochemical.
Result: All new compounds (16 a-f and 19 a-e), were tested with N2, N1 and N1-H274Y and found to be inactive at 2 mM concentration.
Result: Compound
Discovery of C-1 modified oseltamivir derivatives as potent influenza neuraminidase inhibitors.
PMID: 29407952
2018
European journal of medicinal chemistry
Abstract: And its potency against mutant H5N1-H274Y NA was just 7-fold weaker than OSC.
The inhibitory performance of flavonoid cyanidin-3-sambubiocide against H274Y mutation in H1N1 influenza virus.
PMID: 29199545
2018
Journal of biomolecular structure & dynamics
Abstract: A single H274Y mutation induces the conformational changes in the 150th loop which leads to produce more resistance to oseltamivir.
Abstract: Few H1N1 influenza strains with the H274Y mutation creates drug resistance to oseltamivir.
Abstract: In this study, we report that flavonoid cyanidin-3-sambubiocide (C3S) compound acts as a potential inhibitor against H274Y mutation.
Abstract: The drug resistance mechanism and inhibitory activity of C3S and oseltamivir against wild-type (WT) and H274Y mutant-type (MT) have been studied and compared based on the results of molecular docking, molecular dynamics, and quantum chemical methods.
IV mutation literature information.
PMID: 
2019
BMC veterinary research
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