Full Genomic Sequences of H5N1 Highly Pathogenic Avian Influenza Virus in Human Autopsy Specimens Reveal Genetic Variability and Adaptive Changes for Growth in MDCK Cell Cultures.
Result: The H274Y substitution, which indicated the oseltamivir and peramivir resistance, was not present in both the autopsy specimens and the virus isolates, even though the patient received a full course of oseltamivir treatment before his death.
Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus.
Discussion: The detailed molecular mechanism of OTV drug resistance associated with the H274Y mutation in NA can be explained as follows based on the dR
Discussion: The occupancies of the interactions between Y274 and its surrounding residues, including these aromatic residues, remained almost unchanged after the H274Y mutation, except for S246, E276, R292, and H296.
Discussion: The results obtained from the dRIN analysis of the WT and H274Y mutant NA clearly showed that the residue interactions at both the OTV binding site and the H274Y mutation site were partially altered after the mutation.
Discussion: Thus, it leads to a decrease in the binding free energy of the H274Y mutant NA-OTV complex.
Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018-2019.
Discussion: The sequence analysis of the NA gene reveals one potential NA drug-resistance substitution (V116A) but not other amino acid substitutions such as I117V, Q136K, D151A, Y155H, R156K, D198V, I222R, R224K, Q226H, E227D, E227Q, H274Y, R293K, N294S, E425G, and I436N.
Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity.
PMID: 33385836
2021
European journal of medicinal chemistry
Abstract: Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1-H274Y).
Abstract: However, 5c displayed 4.85-fold more potent activity than OSC against H5N1-H274Y NA.
Abstract: Molecular docking studies provided insights into the high potency of 5c against N1 and N1-H274Y mutant NAs.
Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses.
Result: H5N8_E119V and H5N8_H274Y viruses both displayed HRI for PER whereas H5N8_N294S showed a more modest RI to the drug.
Discussion: The H274Y mutation alone resulted in reduced viral fitness but additional
Discussion: The H274Y mutation in all three H5Nx virus backgrounds did not demonstrate any reduction in inhibition for ZAN.
Discussion: The largest effect of the H274Y mutation on susceptibility to OSE and PER was observed with the N8 NA, the only group 1 NA in our panel which agrees with the published literature that the H274Y mutation causes reduced inhibition against OSE and PER for group 1 NAs.
Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus.
PMID: 31773463
2020
Journal of computer-aided molecular design
Abstract: In the present study, all-atom molecular dynamics simulations were applied to understand the oseltamivir resistance caused by the single E119D and double E119D/H274Y mutations on NA.
Reassortment and adaptive mutations of an emerging avian influenza virus H7N4 subtype in China.
Result: Strikingly, no H274Y or R292K in NA changes, which had been associated with oseltamivir resistance, were identified in any of the H7N4 isolates, and not in A/Anhui/1/2013 or partly in A/Shanghai/1/2013, which explained the patient's positive response to oseltamivir treatment and full recovery.
Optimization of 4-Aminopiperidines as Inhibitors of Influenza A Viral Entry That Are Synergistic with Oseltamivir.
PMID: 32069052
2020
Journal of medicinal chemistry
Abstract: Compound 16 displayed a significant decrease of viral titer when evaluated in the infectious assays with influenza virus H1N1 (A/Puerto Rico/8/1934) or H5N1 (A/Vietnam/1203/2004) strains and the oseltamivir-resistant strain with the most common H274Y mutation.
Identification of Chebulinic Acid and Chebulagic Acid as Novel Influenza Viral Neuraminidase Inhibitors.
Abstract: Moreover, oseltamivir-resistance mutation NA/H274Y of NA is susceptible to CHLA or CHLI, suggesting a different mechanism of action for CHLA and CHLI.
Method: Oseltamivir-resistant influenza A/H1N1/pdm(09) virus containing NA/H274Y was provided by Beijing CDC, China, influenza A/Brisbane/10/2007(H3N2) was provided by Chinese Academy of Medical Sciences, and influenza B-Yamagata-like and B-Victoria-like strains were provided by Shandong CDC (Jinan, China).
Result: To compare the antiviral potency of CHLA and CHLI with the marketed NA inhibitor oseltamivir carboxylate, a yield reduction assay was performed with six influenza virus strains, including A/H1N1/PR8, A/H3N2/NY, A/H3N2/Brisbane, B-Yamagate, B-Victoria, and an oseltamivir-resistant A/H1N1pdm(09), which conta
Genetic sequencing of influenza A (H1N1) pdm09 isolates from South India, collected between 2011 and 2015 to detect mutations affecting virulence and resistance to oseltamivir.
PMID: 33154243
2020
Indian journal of medical microbiology
Abstract: Conclusion: In this study, although H274Y mutation associated with oseltamivir resistance has not been noted, significant mutations have been noted in both HA and NA genes including D239N, N295S, V106I, Q136K, N248D, V267A.
IV mutation literature information.
PMID: 
2021
BioMed research international
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