Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses.
PMID: 28433777
2017
European journal of medicinal chemistry
Introduction: Resistance to the only orally available drug, oseltamivir, continues to rise, and the 2008-2009 seasonal H1N1 strain was completely resistant to oseltamivir due to a H275Y mutation.
Result: The viruses tested include multidrug-resistant strains such as the A/Denmark/528/2009 (H1N1), A/Washington/29/2009 (H1N1), and A/Texas/04/2009 (H1N1), all of which are resistant to both amantadine and oseltamivir due to AM2-S31N and H275Y mutations in their M2 and neuraminidase genes, respectively.
Neuraminidase Gene Variations in Influenza A(H1N1)pdm09 Virus among Patients Admitted to Refferal Pulmonary Hospital, Tehran, Iran in 2009-2013.
Abstract: Meanwhile, H275Y substitution, related to oseltamivir resistance, was detected in 3 isolates.
Result: The substitutions were as follows: I17V, A20T, N28D, L40I, L40V, N44S, V62I, S79P, V83M, S95N, D103N, V106I, C124R, R130T, P154S, N200S, G201E, N222D, V241I, N
In vivo mallard experiments indicate that zanamivir has less potential for environmental influenza A virus resistance development than oseltamivir.
PMID: 29139346
2017
The Journal of general virology
Abstract: Our study also adds further evidence regarding the stability of the oseltamivir-induced substitution H275Y without drug pressure, and demonstrates the ability of a H275Y-carrying virus to acquire secondary mutations, further boosting oseltamivir resistance when exposed to zanamivir.
Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2015-2016.
Abstract: As in previous seasons, the most common NA AAS was H275Y in A(H1N1)pdm09 viruses, which confers HRI by oseltamivir and peramivir.
Introduction: In 2007-2008, the unprecedented rise of seasonal A(H1N1) viruses carrying the NA amino acid substitution (AAS) H275Y was detected in Europe; these oseltamivir-resistant viruses rapidly spread globally.
Introduction: In subsequent seasons, A(H1N1)pdm09 viruses containing H275Y NA AAS have been detected in patients with and without exposure to oseltamivir treatment, with large clusters reported in Australia and Japan.
Introduction: The global spread of A(H1N1)pdm09 viruses carrying NA H275Y AAS remains the prime concern for public healt
PMID: 28754164
2017
Journal of translational medicine
Introduction: According to Yang et al., A/H1N1 H275Y variants were seldom isolated in Taiwan until September 2008 when they were found emerging in 14.3% of A/H1N1 isolates.
Introduction: As A/H1N1 subtype progressively prevailed, the proportion of A/H1N1 H275Y strains ultimately reached 100% by the end of year 2008.
Introduction: Given the ever worldwide dissemination of drug-resistant seasonal A/H1N1 H275Y variants during the 2007-2009 influenza seasons, the detection of drug-resistant A/H1N1pdm09 variants was of growing concern.
Introduction: On the other hand, nevertheless, the transmission dynamics of drug-resistant seasonal A/H1N1 H275Y variants was still mysterious at the human population level.
Introduction: The vast majority of A/H1N1 H275Y strains belonged to clade 2B-2, which domina
Characterization of oseltamivir-resistant influenza virus populations in immunosuppressed patients using digital-droplet PCR: Comparison with qPCR and next generation sequencing analysis.
Abstract: Discrimination performance and sensitivity of the RT-ddPCR assay were evaluated using mixes of wild type (WT) and mutated H275Y-NA-coding segments.
Abstract: For the first patient, the H275Y-NA substitution was selected by oseltamivir treatment and reached about 50% of the IV population before dropping to less than 2% after treatment discontinuation which was under the lower limit of quantification by RT-qPCR and RT-ddPCR (<2%) after treatment stop.
Abstract: For the second patient, the H275Y-NA substitution reached about 30% two days after oseltamivir discontinuation.
Abstract: INTRODUCTION: The H275Y substitution in neuraminidase (NA) confers oselt
Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014.
Introduction: From 2007 to 2008, oseltamivir-resistant strains that possessed H275Y mutations in their NA proteins began to emerge within seasonal H1N1 viruses.
Introduction: WHO received the first report regarding an oseltamivir-resistant H1N1pdm2009 isolate in July 2009, and the H275Y mutation within NA was detected in the drug-resistant virus.
Table: H275Y
Discussion: Apart that, the current study revealed that the NA-V241I/N369K/N386K/K432E mutation in conjunction with the H275Y substitution had emerged in the 2013/2014 resistant variants in Guangdong, China.
Discussion: Furth
A Balance between Inhibitor Binding and Substrate Processing Confers Influenza Drug Resistance.
Abstract: NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S, were adaptive in the presence of drug, indicating that our experimental system captured salient features of real-world selection pressures acting on NA.
Antiviral activity of SA-2 against influenza A virus in vitro/vivo and its inhibition of RNA polymerase.
Abstract: In a cytopathic effect assay, SA-2 dose dependently inhibited H1N1, H3N2 and the oseltamivir-resistant mutant H1N1-H275Y influenza viruses in both virus-infected MDCK and A549 cells, with 50% effective concentrations (EC50) in MDCK cells of 9.6, 19.2 and 19.8 muM respectively, and 50% cytotoxic concentration (CC50) of 444.5 muM, showing competitive antiviral activity with oseltamivir in vitro.
Abstract: Orally administered SA-2 effectively protected mice infected with lethal doses of H1N1 or oseltamivir-resistant strain H1N1-H275Y, conferring 70% or 50% survival at a dosage of 100 mg/kg/d, reducing body weight loss, alleviating the influenza-induced acute lung injury, and reducing lung virus titer.
Neuraminidase Activity and Resistance of 2009 Pandemic H1N1 Influenza Virus to Antiviral Activity in Bronchoalveolar Fluid.
Abstract: The oseltamivir resistance mutation H275Y rendered the pandemic H1N1 virus but not the seasonal H1N1 virus more sensitive to BAL fluid.
Abstract: The resistance to the pulmonary innate antiviral activity of the pandemic virus was determined by its neuraminidase (NA) gene, and it was shown that the NA inhibitor resistance mutation H275Y abolished this resistance of the pandemic H1N1 but not the seasonal H1N1 virus, which had compensatory mutations that maintained the fitness of drug-resistant strains.
IV mutation literature information.
PMID: 
2017
European journal of medicinal chemistry
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