Matrix protein 2 of Influenza A virus (M2)

Matrix protein 2 of Influenza A virus (M2) is a small, type III integral membrane protein of 97 amino acids, functioning as a proton-selective ion channel (viroporin) embedded in the viral envelope[1][2][3]. The homotetrameric channel opens in response to endosomal acidification following virus uptake into host cells, enabling protons to enter the virion and promote dissociation of the viral ribonucleoprotein from matrix protein 1, a critical step for viral uncoating and genome release[1][2][3][7]. M2 consists of an extracellular N-terminal domain (M2e), a single transmembrane helix, and a cytoplasmic tail. The proton channel activity is essential for viral replication and is inhibited by the antiviral drugs amantadine and rimantadine, although widespread resistance to these drugs has significantly limited their clinical utility[2][3][7]. Due to the high conservation of its extracellular domain (M2e), M2 is under investigation as a potential target for universal influenza A vaccines[1][7]. M2 also plays roles in virus assembly, budding, and modulation of host cell processes (including inflammasome activation and interference with autophagy)[1][7].

Other names

M2 proteinM2 ion channelAM2 (sometimes used for Influenza A M2 to distinguish from BM2 of Influenza B)M2 proton channel

Blockade of M2 proton channel activity, inhibiting acidification of the viral interior and thus viral uncoating and replication