The M2 channel of influenza A is a target of the adamantane family antiviral drugs. Two different drug-binding sites have been reported: one inside the pore, and the other is a lipid-facing pocket. A previous study showed that a chimera of M2 variants from influenza A and B that contains only the pore-binding site is sensitive to amantadine inhibition, suggesting that the primary site of inhibition is inside the pore. To obtain atomic details of channel-drug interaction, we determined the structures of the chimeric channel with and without rimantadine. Inside the channel and near the N-terminal end, methyl groups of Val27 and Ala30 from four subunits form a hydrophobic pocket around the adamantane, and the drug amino group appears to be in polar contact with the backbone oxygen of Ala30. The structures also reveal differences between the drug-bound and -unbound states of the channel that can explain drug resistance.
Structural investigation of rimantadine inhibition of the AM2-BM2 chimera channel of influenza viruses.,Pielak RM, Oxenoid K, Chou JJ Structure. 2011 Nov 9;19(11):1655-63. PMID:22078564[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
