Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018

Euro Surveill. 2019 Jan;24(3):1800698. doi: 10.2807/1560-7917.ES.2019.24.3.1800698.

Abstract

The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza virus infection in Japan in February 2018. Two influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic subunit (PA) were detected in baloxavir-treated children in December 2018. This mutation is known to confer reduced susceptibility to baloxavir, and the two mutant viruses exhibited 76- and 120-fold reduced susceptibility to baloxavir.

Keywords: Influenza virus; baloxavir acid; baloxavir marboxil; cap-dependent endonuclease inhibitor; resistant.

MeSH terms

  • Amino Acid Substitution / genetics
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Dibenzothiepins
  • Drug Resistance, Viral / drug effects
  • Drug Resistance, Viral / genetics
  • Endonucleases / antagonists & inhibitors*
  • Endonucleases / genetics
  • Humans
  • Influenza A Virus, H3N2 Subtype / drug effects*
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza A Virus, H3N2 Subtype / isolation & purification
  • Influenza, Human / diagnosis
  • Influenza, Human / drug therapy*
  • Japan
  • Microbial Sensitivity Tests
  • Morpholines
  • Oxazines / therapeutic use*
  • Pyridines / therapeutic use*
  • Pyridones
  • Thiepins / therapeutic use*
  • Treatment Outcome
  • Triazines / therapeutic use*

Substances

  • Antiviral Agents
  • Dibenzothiepins
  • Morpholines
  • Oxazines
  • Pyridines
  • Pyridones
  • Thiepins
  • Triazines
  • baloxavir
  • Endonucleases