Antivirals targeting the polymerase complex of influenza viruses

Antiviral Res. 2019 Sep;169:104545. doi: 10.1016/j.antiviral.2019.104545. Epub 2019 Jun 25.

Abstract

Current influenza antivirals have limitations with regard to their effectiveness and the potential emergence of resistance. Encouragingly, several new compounds which inhibit the polymerase of influenza viruses have recently been shown to have enhanced pre-clinical and clinical effectiveness compared to the neuraminidase inhibitors, the mainstay of influenza antiviral therapy over the last two decades. In this review we focus on four compounds which inhibit polymerase function, baloxavir marboxil, favipiravir, pimodivir and AL-794 and discuss their clinical and virological effectiveness, their propensity to select for resistance and their potential for future combination therapy with the most commonly used neuraminidase inhibitor, oseltamivir.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amides / pharmacology
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use*
  • DNA-Directed RNA Polymerases / drug effects*
  • Dibenzothiepins
  • Drug Combinations
  • Drug Resistance, Viral / drug effects
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Influenza A virus / drug effects
  • Influenza B virus / drug effects
  • Morpholines
  • Neuraminidase / antagonists & inhibitors*
  • Orthomyxoviridae / drug effects*
  • Oseltamivir / pharmacology
  • Oxazines
  • Pyrazines / pharmacology
  • Pyridines
  • Pyridones
  • Serine Endopeptidases / pharmacology
  • Thiepins
  • Triazines

Substances

  • Amides
  • Antiviral Agents
  • Dibenzothiepins
  • Drug Combinations
  • Enzyme Inhibitors
  • Morpholines
  • Oxazines
  • Pyrazines
  • Pyridines
  • Pyridones
  • Thiepins
  • Triazines
  • Oseltamivir
  • baloxavir
  • DNA-Directed RNA Polymerases
  • Neuraminidase
  • Serine Endopeptidases
  • sfericase
  • favipiravir