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The anti-influenza virus drug amantadine was shown to reduce the rate of fusion of liposomes with influenza A viruses whose replication is inhibited by this drug. The fusion with amantadine-resistant viruses was unaffected. Experiments with reassortant and mutant viruses showed that this effect was linked to the M2 protein and not to the haemagglutinin of the virus. The proton ionophore monensin, on the other hand, substantially increased the rate of fusion of the viruses tested. These results indicate that the kinetics of virus-liposome fusion can be modulated by the virus M2 protein, the target of amantadine action, and it is postulated that the M2 ion channel functions by transporting protons into the virion interior and facilitating virus uncoating.

Role of virion M2 protein in influenza virus uncoating: specific reduction in the rate of membrane fusion between virus and liposomes by amantadine