Treatment of Highly Pathogenic H7N9 Virus-Infected Mice with Baloxavir Marboxil

Viruses. 2019 Nov 15;11(11):1066. doi: 10.3390/v11111066.

Abstract

Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.

Keywords: H7N9; baloxavir marboxil; highly pathogenic; influenza.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Dibenzothiepins
  • Dose-Response Relationship, Drug
  • Influenza A Virus, H7N9 Subtype / drug effects*
  • Influenza A Virus, H7N9 Subtype / pathogenicity
  • Mice
  • Morpholines
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / virology*
  • Oxazines / pharmacology*
  • Pyridines / pharmacology*
  • Pyridones
  • Thiepins / pharmacology*
  • Triazines / pharmacology*
  • Viral Load
  • Virulence
  • Virus Replication / drug effects

Substances

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