The transmembrane domain of influenza A M2 protein forms amantadine-sensitive proton channels in planar lipid bilayers

In a direct test of the hypothesis that the M2 coat protein of influenza A can function as a proton translocator, we incorporated a synthetic peptide containing its putative transmembrane domain into voltage-clamped planar lipid bilayers. We observed single proton-selective ion channels with a conductance of ∼10 pS at a pH of 2.3, consistent with the association of several monomers around a central water-filled pore. The channels were reversibly blocked by the anti-influenza drug amantadine. These experiments imply a central role for M2 protein in virus replication and assembly and may explain the mechanism of action of amantadine. Analogous proteins may have a similar function in other viruses, and these may be susceptible to similar antiviral agents.