Discussion: Among these NA substitutions, a His-to-Tyr (H274Y) substitution at position 274 is one of the best characterized oseltamivir-resistance markers.
Simultaneous detection and subtyping of H274Y-positive influenza A (H1N1) using pyrosequencing.
PMID: 21628810
2011
Journal of infection in developing countries
Abstract: INTRODUCTION: We investigated the frequency of H274Y-positive swine-origin 2009 A (H1N1) influenza virus outbreak in Thailand during May-August 2009.METHODOLOGY: This study sought to find Oseltamivir resistance mutation H274Y by using pyrosequencing.
Abstract: RESULTS: From 8,710 real-time RT-PCR swine-origin 2009 A(H1N1) influenza virus-positive specimens, 100 randomly selected samples identified one such virus with H274Y mutationusing pyrosequencing.
Neuraminidase inhibitor R-125489--a promising drug for treating influenza virus: steered molecular dynamics approach.
PMID: 21693105
2011
Biochemical and biophysical research communications
Abstract: Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems.
Study of Tamiflu sensitivity to variants of A/H5N1 virus using different force fields.
PMID: 21834591
2011
Journal of chemical information and modeling
Abstract: GROMOS96 43a1 provides a lower correlation as it supports Oseltamivir to be more resistant to N294S than H274Y.
Abstract: In this paper, we consider the impact of four main force fields, AMBER99SB, CHARMM27, GROMOS96 43a1, and OPLS-AA/L, on the binding affinity of Oseltamivir carboxylate to the wild-type and Y252H, N294S, and H274Y mutants of glycoprotein neuraminidase from the pandemic A/H5N1 virus.
Abstract: They correctly capture the binding ranking Y252H WT N294S H274Y observed in experiments (Collins, P.
Role of permissive neuraminidase mutations in influenza A/Brisbane/59/2007-like (H1N1) viruses.
Introduction: The H275Y (H274Y in N2 numbering) NA mutation conferring resistance to oseltamivir and peramivir has been detected with increasing frequency in seasonal A/H1N1 viruses since 2007 to the extent that almost all characterized A/Brisbane/59/2007-like (Bris07) (H1N1) influenza strains that circulated worldwide during the 2008-09 season were H275Y variants.
[Oseltamivir resistance depends on the position 273 amino acid of neuraminidase of the type A influenza virus (H1N1), circulating in human population].
Abstract: Phenylalanine at position 273 in neuraminidase indicates a higher propensity to influenza virus mutation H274Y, leading to the appearance of resistant strains.
Evaluation of a rapid molecular algorithm for detection of pandemic influenza A (H1N1) 2009 virus and screening for a key oseltamivir resistance (H275Y) substitution in neuraminidase.
Abstract: Mutations at D151 without H274Y, did not elevate IC(50) for any tested NAI, however, Q136K alone significantly reduced susceptibility to zanamivir (36-fold), peramivir (80-fold) and A-315675 (114-fold) but not oseltamivir.
Abstract: Pyrosequencing analysis confirmed H274Y mutation (H275Y in N1 numbering) in the neuraminidase (NA) gene of oseltamivir-resistant viruses.
Abstract: Viruses with very high IC(50) for oseltamivir and peramivir, and elevated IC(50) for zanamivir, had H274Y in addition to mutations at D151 and/or Q136, residues which can potentially confer NAI resistance based on recent N1 NA crystal structure dat
Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008-2009 season.
Abstract: CONCLUSIONS: A dramatic surge in oseltamivir-resistant A(H1N1) viruses possessing the NA-H274Y substitution was detected in Japan during the 2008-2009 season.
Abstract: Oseltamivir resistance was determined by an H274Y-specific real-time PCR cycling probe assay and a neuraminidase inhibition assay.
Abstract: RESULTS: Three of 687 (0.4%) A(H1N1) viruses from the 2007-2008 season and 745 of 745 (100%) viruses from the 2008-2009 season carried the NA-H274Y substitution and demonstrated a >300-fold reduction in oseltamivir susceptibility.
Laninamivir prodrug CS-8958, a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration.
PMID: 20047917
2010
Antimicrobial agents and chemotherapy
Abstract: CS-8958 also significantly reduced the titers of an oseltamivir-resistant H1N1 virus with a neuraminidase H274Y substitution in a mouse infection model.