Matrix-2 (M2) protein (M2)

The **Matrix-2 (M2) protein** is a small, 97-amino-acid, single-pass membrane protein from the influenza A virus that forms a tetrameric, proton-selective ion channel (viroporin) in the viral envelope[5][1][3][6]. Upon entry of the virus into host cells, the low pH of the endosome activates the M2 channel, allowing protons to enter the virion and thereby promoting uncoating of the viral ribonucleoprotein complex—a critical step for viral genome release and replication[1][5][3]. M2 also helps maintain pH balance within intracellular compartments during viral assembly, preventing premature conformational changes of the viral hemagglutinin protein[3][9]. Its proton channel activity is essential for influenza A virus replication[5]. The M2 protein is the molecular target of adamantane-class antiviral drugs (amantadine and rimantadine), which inhibit its channel function and thus block the viral replication cycle; however, resistance due to mutations such as S31N is now widespread[1][5][3]. M2 has a key His37 residue acting as the channel's selectivity filter and a Trp41 residue functioning as a gate; the amphipathic helix in the cytoplasmic tail additionally participates in viral budding and assembly[5][6]. Homologous proteins exist in influenza B (BM2) and C (CM2) viruses, but only the influenza A M2 is sensitive to adamantane drugs[3][7].

Other names

Influenza A M2 proteinM2 proton channelAM2

Blockade of proton conduction by binding in the channel pore (amantadine/rimantadine); Inhibition of viral uncoating and replication by preventing the acidification of the viral interior