Influenza A virus M2 proton channel (M2)

The **Influenza A virus M2 proton channel** is a small, tetrameric, pH-gated, proton-selective ion channel encoded by the influenza A virus. It forms an integral membrane viroporin within the viral envelope, essential for viral replication, infectivity, and uncoating. Upon host entry, acidic pH in endosomes activates the channel, allowing protons into the virion core, which triggers dissociation of the viral ribonucleoprotein complex and releases viral genetic material into host cytoplasm for replication. The M2 protein also prevents premature conformational changes of hemagglutinin during viral maturation. It is a validated antiviral drug target; amantadine and rimantadine inhibit its activity by blocking proton conduction, but resistance to these drugs is common due to high-frequency mutations in the M2 transmembrane domain[1][3][4][7]. Key structural features include: - Homotetrameric assembly through the transmembrane domain. - N-terminal extracellular domain, a central transmembrane proton-conducting helix, and a C-terminal cytoplasmic tail. - pH sensor His37 and gate Trp41 are key residues in proton selectivity and channel gating[7]. M2 serves as a critical determinant in the influenza A life cycle and is under intensive research for novel inhibitors due to resistance against existing drugs[4][7].

Other names

M2 proteinMatrix 2 proteinAM2

Blockade of proton conductance (amantadine, rimantadine); Inhibition of viral uncoating; Prevention of viral RNA release