Influenza A matrix protein 2 ion channel (M2)

The Influenza A matrix protein 2 ion channel (M2 protein) is a small, integral viral membrane protein consisting of 97 amino acids, forming a homotetrameric, pH-gated, proton-selective channel. The channel is essential for the viral life cycle, allowing protons to enter the virion upon endosomal acidification. This acidification enables uncoating of the viral genome for replication. M2 also regulates pH balance in the Golgi during late viral assembly, preventing premature activation of hemagglutinin. The protein's transmembrane domain constitutes the core of its ion channel function and is the principal binding site of approved drugs like amantadine and rimantadine, although resistance (especially via the S31N mutation) is now common. Structurally, M2 channels are an important model for membrane protein function and inhibition. Its role makes it a prime target for antiviral intervention, but therapeutic challenges remain due to prevalent drug resistance and side effects.

Other names

M2 proteinM2 proton channelMatrix protein 2IAV M2AM2Influenza A M2 channel

Channel blockade — Drugs such as amantadine and rimantadine bind to the pore formed by the tetrameric transmembrane domain, inhibiting proton conductance and thus blocking viral uncoating and replication.