Molecular basis of resistance of influenza A viruses to amantadine

Amantadine (1-aminoadamantane hydrochloride) is effective in the prophylaxis and treatment of influenza A infection. In tissue culture this selective, strain-specific antiviral inhibits either the initiation of infection or virus assembly. The basis of these actions is similar and both the haemagglutinin and M2 proteins are implicated suggesting that amantadine interferes with their functions or the interactions between these two virus proteins. Mutations which confer resistance to amantadine are restricted to four amino acids within a hydrophobic sequence of M2 indicating that the primary target of drug action is the membrane-associated portion of this molecule.