Influenza A M2 proton channel (M2)

The Influenza A M2 proton channel is a homotetrameric, integral membrane ion channel found in the viral envelope of all influenza A virus strains[1][7]. It forms a proton-selective channel activated by low pH, playing a critical role in viral entry by mediating the acidification of the interior of endocytosed virions. This acidification triggers the release of viral ribonucleoproteins from matrix proteins, facilitating viral genome release for replication upon fusion with the host cell membrane[1][2][4][7][10]. Structurally, the M2 protein consists of an extracellular N-terminal domain, a transmembrane helix (which forms the ion-conducting pore), and a C-terminal cytoplasmic domain involved in membrane scission during virus budding[1][7]. The channel is a clinically validated antiviral target, historically inhibited by adamantane derivatives such as amantadine and rimantadine. However, resistance-conferring mutations (e.g., S31N) have become widespread, necessitating ongoing development of new channel inhibitors[3][6]. The M2 proton channel remains a paradigm for structure–function investigations of viroporins and antiviral drug design.

Other names

Matrix-2 proteinM2 proteinInfluenza A virus M2

Blockade of proton conductance through the M2 channel, thereby preventing acidification of the influenza virion interior and subsequent uncoating required for viral replication. Disruption of viral assembly and budding by interfering with the channel's role in membrane scission.