Targeted inhibition of the endonuclease activity of influenza polymerase acidic proteins

Future Med Chem. 2022 Apr;14(8):571-586. doi: 10.4155/fmc-2021-0264. Epub 2022 Feb 25.

Abstract

Influenza is a type of acute respiratory virus infection caused by the influenza virus that occurs in epidemics worldwide every year. Due to the increasing incidence of influenza virus resistance to existing drugs, researchers are looking for novel antiviral drugs with new mechanisms. The endonuclease activity of polymerase acidic protein is essential in the process of influenza virus reproduction, and inhibiting it could prevent the virus from replicating. There are relatively few drugs that act on this protein, and only baloxavir marboxil has been approved for clinical use. In this article, the structure and function of influenza virus polymerase acidic protein endonuclease, mechanism of action of polymerase acidic endonuclease inhibitors and the research progress of inhibitors are reviewed.

Keywords: PA inhibitors; drug target; influenza viruses; polymerase acidic protein endonuclease inhibitors; research progress.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral
  • Endonucleases / metabolism
  • Endonucleases / pharmacology
  • Humans
  • Influenza, Human* / drug therapy
  • Pyridones / pharmacology
  • Triazines / pharmacology
  • Viral Proteins

Substances

  • Antiviral Agents
  • Pyridones
  • Triazines
  • Viral Proteins
  • Endonucleases