Discussion: Each one oseltamivir and peramivir cross-resistant A/H3N2 virus with the R292K mutation was detected in the 2010-11, 2011-12, and 2014-2015 seasons, respectively.
Discussion: Here, we demonstrated the first case of successful treatment using baloxavir for the dual E119D/R292K NA-mutated peramivir-resistant influenza A/H3N2 in a highly immunocompromised patient.
Discussion: In the global surveillance, the frequency of viruses with reduced susceptibility to one or more NA inhibitors has remained low (2012-13: 0.6%; 2013-14: 1.9%; 2014-15: 0.5%; 2015-16: 0.8%; 2016-17: 0.2%), while oseltamivir and peramivir cross-resistant A/H1N1pdm09 viruses with an NA H275Y substitution were the most frequently observed.
Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea.
Abstract: RESULTS: Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer.
Introduction: However, since most recently detected type A influenza viruses harbor the resistance variation S31N in the matrix gene, the M2 proton-channel blockers amantadine and rimantadine are no longer clinically applied.
Introduction: The typical drug-resistance substitutions in NA include H275Y, E119D/G, and Q136R for A(H1N1)pdm09; E119V, D151G/V/D,
Enhanced Potency of a Broad H7N9-Neutralizing Antibody HNIgGA6 Through Structure-Based Design.
Figure: (B) S28H neutralized 11 out of the total 12 strains tested.
Figure: Enhancement of in vitro neutralizing potency for the S28H variant.
Figure: Enhancement of viral HA binding affinity for the S28H mutant.
Figure: Increased in vivo neutralization potency of the S28H variant.
Figure: Less dramatic pathological changes in the lungs of the S28H-treated mice were detected One-way ANOVA was used to analyze the data (ANOVA, F = 70.52, p = 2.32E-07).
Figure: Mice received HNIgGA6 or S28H mAb 24 h before H7N9 infection and were monitored daily for 14 days.
Figure: Mice were passively immunized with HNIgGA6 or S28H variant 24 h and then challenged with a lethal dose of H7N9 vir
Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts.
PMID: 32640124
2020
The New England journal of medicine
Abstract: In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively.
Identification of a Permissive Secondary Mutation That Restores the Enzymatic Activity of Oseltamivir Resistance Mutation H275Y.
Abstract: We report A4 antibody specifically recognizing and binding to the mutant I223R/H275Y neuraminidase and prove the applicability of A4 antibody for direct detection of antiviral multidrug-resistant viruses in various sensing platforms, including naked-eye detection, surface-enhanced Raman scattering-based immunoassay, and lateral flow system.
Introduction: According to the experimental and simulation results, the binding affinity of A4 for oseltamivir- and zanamivir-resistant mutant I223R/H275Y NA is approximately 600 times stronger than its binding affinity for oseltamivir- and zanamivir-susceptible wild-type (wt) NA.
Introduction: Here we develop a monoclonal antibody, A4, specific to I223R<
Influenza A virus NS1 optimises virus infectivity by enhancing genome packaging in a dsRNA-binding dependent manner.
Abstract: For comparison, K6 and K17 were found to be dissimilar for various mutations, such as A274T of PB2, S375N/T of PB1, or V105M of NP, each concerning the increased virulence of K6 in mammalian system.
Abstract: However, molecular analysis revealed the E119V mutation in the NA gene and a human host marker mutation E382D in the polymerase acidic (PA) gene, implying their susceptibility to neuraminidase inhibitors and potential infectivity in humans, respectively.
Discussion: According to the molecular analysis of gene segments between K6 and A/aquat
Structural Basis of Human Helicase DDX21 in RNA Binding, Unwinding, and Antiviral Signal Activation.
5Result: Finally, the ""3R to A"" mutant lost most of the unwinding activity, whereas the Asp321Ala mutant had comparable unwinding activity (Figure 5F)."
Result: A similar increase of ATP binding for DEAD mutants was observed in DEAD-box helicase elF-4A.[26] However, in contrast to the increase of ATP binding by Asp339His mutation, the Glu340Gly mutation lost the inter-domain interaction with Arg499 and His523 (Figure 3F).
Result: As shown in Figure6A, the RNA-binding defective mutant of DDX21 (4R to A) was associated with less of NS1 while the DDX21 DEV mutant (Asp339His, Glu340Gly) could pull-down more NS1 protein than WT DDX21.
Abstract: The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness.
Abstract: The objective of this work was to compare the fitness of two strains of OR (R6 and R7) containing the H275Y mutation, and a wild-type (F) pandemic influenza A (H1N1) 2009 (pdm09) virus both in vitro and in vivo in mice and to select one OR strain for a comparison with F in ferrets.
Introduction: Among such NA substitutions, a histidine-to-tyrosine substitution at position 275 (H275Y) is one of the best-characterized and most commonly found oseltamivir-resistant (OR) mutations.
Introduction: De
Method: The A/Baleares/RR6121/2009 and A/Madrid/RR7495/2011 viruses bear the OR H275Y mutation and are hereafter referred to as R6 and R7, respectively.
Design and synthesis of pinane oxime derivatives as novel anti-influenza agents.
Abstract: Currently, to design non-adamantane compounds targeting the S31N mutant of M2 proton channel is a promising direction for the development of novel anti-influenza drugs.
Abstract: In our previous research, a pinanamine-based antiviral M090 was discovered to target hemagglutinin instead of M2, with its structure being highly similar to reported M2-S31N inhibitors.
Abstract: Utilizing a combination of structure-activity relationship analysis, electrophysiological assay and molecular docking, the most potent compound 11h, as a M2-S31N blocker, exhibited excellent activity with EC50 value at the low micromolar level against both H3N2 and H1N1.
IV mutation literature information.
PMID: 
2020
BMC infectious diseases
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