Acidified Influenza A Viral Particle Docked At The Endocytic Vesicle Membrane With An Open Pore Influenza A Viral Particle Docked At The Endocytic Vesicle Membrane With An Open Pore Virion-associated M2 protein mediated ion infusion GENE ONTOLOGYGO:0019061 Pubmed563896 Pubmed7688826 Pubmed8841994 Reactome Database ID Release 43168313 Reactome, http://www.reactome.org ReactomeREACT_6315 The uncoating of influenza viruses in endosomes is blocked by changes in pH caused by weak bases (e.g. ammonium chloride and chloroquine) or ionophores (e.g. monensin). Effective uncoating is also dependent on the presence of the viral M2 ion channel protein. Early on it was recognized that amantadine and rimantadine inhibit replication immediately following virus infection. Later it was found that the virus-associated M2 protein allows the influx of H+ ions from the endosome into the virion. This disrupts protein-protein interactions, resulting in the release of viral RNP free of the viral matrix (M1) protein. Amantadine and rimantadine have been shown to block the ion channel activity of the M2 protein and thus uncoating.