Influenza A virus polymerase acidic protein E23R substitution is a marker of reduced susceptibility to baloxavir

Antiviral Res. 2022 Aug:204:105369. doi: 10.1016/j.antiviral.2022.105369. Epub 2022 Jun 20.

Abstract

In our ongoing efforts to identify baloxavir resistance markers, we demonstrated that the influenza A polymerase acidic (PA) protein E23R substitution is genetically stable, increases baloxavir EC50 values (13- to 19-fold vs. wild-type), synergizes with PA I38T, and only modestly decreases viral fitness. E23R is, therefore, a potential threat to baloxavir treatment efficacy.

Keywords: Antiviral; Baloxavir; E23R; Endonuclease; Influenza; Polymerase acidic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Substitution
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Dibenzothiepins
  • Drug Resistance, Viral / genetics
  • Humans
  • Influenza A virus* / genetics
  • Influenza, Human* / drug therapy
  • Morpholines
  • Oxazines / pharmacology
  • Oxazines / therapeutic use
  • Pyridines / pharmacology
  • Pyridones / pharmacology
  • Pyridones / therapeutic use
  • Thiepins* / pharmacology
  • Thiepins* / therapeutic use
  • Triazines / pharmacology
  • Triazines / therapeutic use

Substances

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