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)).
Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza a virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.
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.
Figure: Clinical course in a severely immunosuppressed patient with peramivir-resistant dual E119D/R292K neuraminidase mutated-influenza A/H3N2 after allo-HCT allo-HCT, allogeneic hematopoietic cell transplantation; A-VVV, cytosine arabinoside, etoposide, vincristine, and vinblastine; CsA, cyclosporine A; HU, hydroxyurea; Lym, lymphocyte; PSL, prednisolone.
Discussion: The patient developed seasonal influenza A/H3N2 infection while in a highly immunocompromised state post-transplant-relapsed leukemia; treatment with 1-day oseltamivi
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.
Continuing evolution of H6N2 influenza a virus in South African chickens and the implications for diagnosis and control.
Result: Six mutations are associated with the acquisition of resistance to neuramindase inhibitors, namely E119V, R152K, D198N, H274Y, R292K and N294S.
A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses.
Result: Meanwhile, R292K, a mutation attributed to neuraminidase inhibitor (NAi) resistance, was identified in GD17 NA.
Highly pathogenic avian influenza H7N9 viruses with reduced susceptibility to neuraminidase inhibitors showed comparable replication capacity to their sensitive counterparts.
Abstract: CONCLUSIONS: All 4 amino acid substitutions (R292 K, E119V, A246T or H274Y) in NA reduced the susceptibility of HPAI H7N9 to NAIs.
Abstract: RESULTS: Four potential NAI resistance sites, R292 K,
Conclusion: As a result, all 4 amino acid substitutions (R292 K, E119V, A246T or H274Y) in the NA protein reduced the susceptibility of HPAI H7N9 to oseltamivir or zanamivir.
Evolved avian influenza virus (H7N9) isolated from human cases in a middle Yangtze River city in China, from February to April 2017.
Result: A number of H7N9 viruses had acquired Arg292Lys substitution associated with oseltamivir-resistance in NA gene until April 2017.
Result: But Arg292Lys substitution was not observed, and antivirals including oseltamivir were still administrated to all patients with H7N9 infections in our research.
Table: Arg292Lys
Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection.
PMID: 29688498
2018
The Journal of infectious diseases
Abstract: Neuraminidase (NA) R292K, basic polymerase 2 (PB2) E627K, and D701N were the 3 most dynamic mutations.
Abstract: The oseltamivir resistance-related NA R292K mutation was present in 9 samples from 5 patients, including 1 sample obtained before antiviral therapy.
Discussion: A previous study indicated that the introduction of the R292K mutation into the NA segment leads to competitive fitness loss by avian H7N9 influenza virus.
Discussion: A previous study showed that NA R292K emerged under antiviral pressure conferred by PMID: 29563296
2018
Journal of virology
Abstract: Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains.
Abstract: Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections.
Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes.
Abstract: In addition, two substitutions, H274Y and R292K (N2 numbering), were introduced into each NA gene for comparison.
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).
IV mutation literature information.
PMID: 
2020
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