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.
Baloxavir Marboxil in Japanese Pediatric Patients With Influenza: Safety and Clinical and Virologic Outcomes.
Abstract: Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer).
Abstract: CONCLUSIONS: A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children.
Abstract: Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses).|m
Human-to-Human Transmission of Influenza A(H3N2) Virus with Reduced Susceptibility to Baloxavir, Japan, February 2019.
Conclusion: Almost all mutant viruses isolated from baloxavir-treated patients possessed mixed PA I38T/I, I38M/I, I38R/I, I38T/M/I, I38T/K/I, or I38T/M/R substitutions, indicating these mutant viruses emerged under the selective pressure of ba
Introduction: In phase 2 and 3 clinical trials of baloxavir, treatment-emergent amino acid substitutions--I38T or I38F for influenza A(H1N1)pdm09 (pH1N1) virus and I38T or I38M for influenza A(H3N2) virus in the polymerase acidic (PA) protein--were detected.
Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019.
Discussion: A previous study reported that influenza A/Victoria/3/75(H3N2) viruses with the PA I38T, I38M, or I38F substitutions showed less growth capability than the wild-type virus in cell culture.
Discussion: Among the 11 persons infected with PA I38T or I38M mutant A(H3N2) viruses in the 2018/19 season in Japan, all but one were children younger than 12 years.
Discussion: Deep sequencing analysis revealed that eight of these viruses possessed mixed PA I38T/I or I38T/M/I substitutions in the clinical specimens and six of these eight possessed increased
Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018.
Introduction: In Phase II and III clinical trials, I38T, I38F and I38M substitutions in the polymerase acidic subunit (PA) were detected in A(H1N1)pdm09 and A(H3N2) influenza viruses.
Discussion: Furthermore, influenza A/Victoria/3/75(H3N2) viruses with the PA I38T or I38M substitutions showed 56.6- and 13.8-fold higher EC50 values, respectively.
Discussion: In the Phase III trials, the PA I38T and I38M substitutions emerged in 36 (9.7%) of 370 A(H3N2) viruses obtained from patients aged 12-64 years and in 18 (23.4%) of 77 A(H3N2) viruses obtained from children aged 6 months to < 12 years.
Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil.
Introduction: In a Phase III clinical trial, PA I38T and I38M substitutions were detected after exposure to this drug in 9.7% of 370 A(H3N2) viruses.
Introduction: In a pediatric study, PA I38T and I38M substitutions emerged in 18(23.4%) of 77 A(H3N2) viruses.
Introduction: Patients infected with the PA I38T or I38F mutant viruses exhibited prolonged virus shedding and the median time to alleviation of symptoms was longer in baloxavir recipients with I38T or I38M substitutions than in those without substitutions.
Discussion: In contrast, influenza B viruses with the
Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.
Result: By comparison, for rgB/Maryland/1/59, I38F conferred impaired replicative capacity, whereas I38T and I38M viruses were comparable to the wild-type.
Result: Collectively, I38T and I38M in A/H3N2 viruses were identified by the treatment-emergent monitoring of the pediatric study as conferring more than 10-fold reductions in BXA susceptibility, whereas A37T and E199G had lesser effects.
Result: Drug testing showed that the FCs of A/H3N2 with the single mutation of I38T or I38M were 56.59 and 13.77-fold, respectively (Table 1).
Result: In MDCK cells, the viral titers of rgA/WSN/33 with I38T, I38F
A combination of HA and PA mutations enhances virulence in a mouse-adapted H6N6 influenza A virus.
IV mutation literature information.
PMID: 
2020
Antiviral research
Browser Board
Co-occurred Entities
Filtrator
ViMRT