Matrix protein 2 (M2) (M2)

Matrix protein 2 (M2) is a homotetrameric integral membrane protein essential for the replication cycle of the Influenza A virus. It functions as a pH-gated, proton-selective ion channel that equilibrates the pH across the viral envelope during endocytosis (UniProt [2], Wikipedia [14]). This acidification triggers the dissociation of the viral ribonucleoprotein (vRNP) from the matrix protein 1 (M1), allowing the viral genome to enter the host cell cytoplasm for replication (PMC [12]). Additionally, M2 plays a vital role in viral assembly and budding and prevents the premature conformational change of hemagglutinin by regulating the pH of the trans-Golgi network (PubMed [7], ResearchGate [8]). Historically, M2 has been the target of adamantane-class antiviral drugs like amantadine and rimantadine, which block the channel's pore to prevent infection (Patsnap Synapse [3]). However, widespread resistance mutations, particularly the S31N amino acid substitution, have significantly reduced the clinical utility of these drugs in modern seasonal influenza treatment (PubMed [7], MDPI [1]).

Other names

M2 ion channelMatrix-2 proteinProton-selective ion channel M2Viroporin M2Proton channel protein M2AM2

M2 channel blockers bind within the transmembrane pore of the homotetrameric M2 protein, physically obstructing the channel and preventing the influx of protons from the endosome into the viral interior; this inhibition prevents the dissociation of the viral ribonucleoprotein from the matrix protein 1, thereby halting viral uncoating and genome release into the host cell cytoplasm.