Result: Six mutations are associated with the acquisition of resistance to neuramindase inhibitors, namely E119V, R152K, D198N, H274Y, R292K and N294S.
Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection.
PMID: 29688498
2018
The Journal of infectious diseases
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, E276D, R292K, N294S, and R371K (N2 numbering).
Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and -2 Influenza A Neuraminidases, Including a Drug-Resistant Variant.
PMID: 29965752
2018
Journal of medicinal chemistry
Abstract: They also showed greater inhibitory activity than OSC toward H274Y and E119V variant.
Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil.
Result: The influenza A(H1N1)pdm09-NA/H275Y, A(H3N2)-NA/E119V or -NA/R292K, and influenza B-NA/D197E mutant viruses exhibited HRI or RI against at least one of the four NA inhibitors, whereas no significant differences in baloxavir susceptibilities were found between the NA inhibitor-resistant and wild-type viruses by using either assay (Table 2); however, influenza B viruses showed higher IC50 values than influenza A viruses, as previously reported.
Table: E119V
Influenza A/H3N2 virus infection in immunocompromised ferrets and emergence of antiviral resistance.
Result: Mutation E119V was not detected in these samples, whereas the R292K resistance mutation was detected in the nose and throat swabs of all immunocompromised (Fig 2C) ferrets that were treated with Oseltamivir.
Result: Samples from all inoculated animals (Fig 2 and S3 Fig) were analyzed by mutation-specific RT-PCR to detect substitutions E119V and R292K in NA, the most common Oseltamivir associated resistance mutations in A/H3N2 influenza viruses.
Discussion: The R292K substitution was found to cause a greater reduction in susceptibility to Oseltamivir compared to the E119V substitution, conferring a > 9000 increase of the Oseltamivir IC50.
Discussion: This could explain why the E119V mutat
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: 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.
Neuraminidase inhibitor susceptibility and neuraminidase enzyme kinetics of human influenza A and B viruses circulating in Thailand in 2010-2015.
Discussion: However, the I222V NA substitution has a compensatory effect on the influenza A(H3N2) virus carrying E119V, and the presence of these two substitutions resulted in partially improved viral fitness in cell culture and resistance to oseltamivir.
Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes.
Abstract: Substitutions conferring NAI resistance were mainly categorized as either novel NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K).
Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2015-2016.