Discussion: Some mutations such as E119D/Q, H274Y/R or N294S, albeit rare in avian isolated H5Nx viruses, were found to have naturally arisen (Table 1) and we would predict that the strains we identified in the database of the H5N6 and H5N8 subtype with an alternative E119 residue in the NA coding region and the H5N6 H274Y mutation would result in these viruses having functionally reduced susceptibility to OSE.
Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea.
Introduction: The typical drug-resistance substitutions in NA include H275Y, E119D/G, and Q136R for A(H1N1)pdm09; E119V, D151G/V/D, R224K, E276D, R292K, and N294S for A (H3N2); and G104E, E117A/D, H134Y, and R150K for B virus, although additional single and combination mutations may also result in NAI drug resistance (World Health Organization (WHO)).
Source of oseltamivir resistance due to single E119D and double E119D/H274Y mutations in pdm09H1N1 influenza neuraminidase.
Abstract: Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2.
Abstract: To our knowledge, no report is available on the clinical course of a severe
Conclusion: We examined the HD15-influenza-positive sample by polymerase chain reaction and sequence analysis, which detected a dual E119D/R292K mutant influenza A/H3N2.
Introduction: Here, we demonstrate that baloxavir marboxil (hereafter referred to as baloxavir), a new selective inhibitor of influenza cap-dependent endonuclease, was effective in a highly immunocompromised patient with peramivir-resistant dual E119D/R292K NA mutated-influenza A/H3N2 after allo-HCT.
Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017-2018.
Abstract: PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23G/K/R, PA A36V, PA A37T, PA I38F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions.
Source of oseltamivir resistance due to single E119D and double E119D/H274Y mutations in pdm09H1N1 influenza neuraminidase.
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.
Highly pathogenic avian influenza H7N9 viruses with reduced susceptibility to neuraminidase inhibitors showed comparable replication capacity to their sensitive counterparts.
Introduction: The research demonstrated that R292K and H274Y conferred a high increase in oseltamivir IC50, and E119D conferred the highest IC50 to zanamivir reported.
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).
Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.
Result: It has been reported that PA E119D confers resistance to the compound L-742,001 that targets the CEN with a metal chelating mechanism similar to BXA.
Result: Of note, variants with E119D or E120D were not detected so far in the BXM clinical studies.
Result: We found that E119D conferred slightly reduced susceptibility to BXA by 6.46 and 4.51-fold in A/H1N1 and A/H3N2, respectively, while E120D in type B virus did not have a significant impact (Table 1).
Result: We therefore evaluated the antiviral effect of BXA to type A and B viruses with the PA mutations E119D and E120D, respectively.
Table: E119D
Identification of the I38T PA Substitution as a Resistance Marker for Next-Generation Influenza Virus Endonuclease Inhibitors.
Introduction: A random mutagenesis approach in the PR/8 or A/California/04/2009 (H1N1)pdm09 (CA/04) background identified PA-T20A, -
Introduction: In the case of the E119D substitution, the holoenzyme only has one bound metal ion at the two-metal active site, but the second metal ion is restored to the active site by the coordinating groups provided by RO-7, as seen in the E119D-L-742,001 complex.
Introduction: Sequence encoding a loop-deleted version (residues 51 to 72 replaced with a GGS linker) of the PAN WT or the point mutation (I38T or E119D) from CA/04 was synthesized and inserted in pET-28a(+) expression plasmid (Genescript, Piscataway, NJ), expressed in BL21(DE3) cells, and purified by affinity chromatography and gel filtration (Protein Production Facility, SJCRH).
Amino acid substitutions in the neuraminidase protein of an H9N2 avian influenza virus affect its airborne transmission in chickens.
Discussion: It was found that the NA activity of A/Moscow/10/99 (H3N2) influenza virus with D198N and E119D mutations in NA was considerably lower than for the parental virus following stable passage in MDCK cells.
Discussion: reported that D198N, E119D and I222L mutations in NA of H3N2 influenza virus could alter the biological activity of NA.
IV mutation literature information.
PMID: 
2020
Antiviral research
Browser Board
Co-occurred Entities
Filtrator
ViMRT