Influenza A virus M2 proton channel protein (M2 protein (M2))

The Influenza A virus M2 protein is a small (97-residue) single-pass transmembrane proton channel (viroporin) embedded in the viral envelope, assembled as a pH-gated homotetrameric complex. It plays two central roles in the viral lifecycle: acidification of the viral interior during entry (to trigger genome release) and maintenance of the trans-Golgi pH during viral assembly, preventing premature activation of the hemagglutinin protein. The transmembrane segment forms the ion-conducting pore, where proton conductance is primarily governed by His37 (pH sensor) and Trp41 (gate). The M2 channel is the molecular target of the adamantane antivirals amantadine and rimantadine, but widespread resistance due to mutations (most prominently S31N) has limited their clinical utility. M2 is considered a classical antiviral drug target and remains a focus for the development of new inhibitors to address drug-resistant influenza A strains[1][2][3][4][5][6][7][8].

Other names

Matrix-2 proteinInfluenza A M2 proteinAM2M2 ion channel

Blockade of viral proton channel function; Inhibition of viral uncoating inside host endosome; Inhibition of viral assembly and release (by disrupting budding roles)