Put a cork in it: Plugging the M2 viral ion channel to sink influenza

Antiviral Res. 2020 Jun:178:104780. doi: 10.1016/j.antiviral.2020.104780. Epub 2020 Mar 27.

Abstract

The ongoing threat of seasonal and pandemic influenza to human health requires antivirals that can effectively supplement existing vaccination strategies. The M2 protein of influenza A virus (IAV) is a proton-gated, proton-selective ion channel that is required for virus replication and is an established antiviral target. While licensed adamantane-based M2 antivirals have been historically used, M2 mutations that confer major adamantane resistance are now so prevalent in circulating virus strains that these drugs are no longer recommended. Here we review the current understanding of IAV M2 structure and function, mechanisms of inhibition, the rise of drug resistance mutations, and ongoing efforts to develop new antivirals that target resistant forms of M2.

Keywords: Drug discovery; Drug resistance; Electrophysiology; Influenza; M2; Viroporin.

Publication types

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

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / metabolism
  • Adamantane / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Drug Development
  • Drug Discovery
  • Drug Resistance, Viral
  • Humans
  • Influenza A virus / drug effects*
  • Influenza A virus / physiology
  • Influenza, Human / drug therapy*
  • Influenza, Human / virology
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / metabolism
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / virology
  • Viral Matrix Proteins / antagonists & inhibitors*
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Ion Channels
  • M2 protein, Influenza A virus
  • Viral Matrix Proteins
  • Adamantane