As for BI-D1870 inhibitor A4, no bioactivity data to M2 proton channel was reported. The designed inhibitor A5 has two (+)-JQ1 pharmacophore groups: a hydroxyl group on position 2 and an amino group on position 3 of adamantane. Illustrated in Fig. 6 is a close view of the interactions between the designed inhibitor A5 and the M2 proton channel. The amino group of inhibitor A5 binds at the carboxyl group of 1Asp44 of Chain-1 through two hydrogen bonds, while the second pharmacophore hydroxyl group forms two hydrogen bonds with the amino group of 2-Arg45 of Chain-2. The NMR structure of M2 proton channel provides a reliable structural basis for rational drug design against influenza virus. The channel gating mechanism and the inhibiting mechanism of M2 proton channel, revealed by the NMR structure of M2 proton channel, stimulate the new idea and strategy for channel inhibitor design. The two inhibitors of M2 proton channel, designed in this study, are hopefully the potential drugs for the 2009-H1N1 swine flu. The adamantane-based drugs are not like the ordinary drug molecules from the viewpoint of Lipinski��s “the rule of five”, a rule of thumb to evaluate druglikeness, or to determine if a chemical compound with a certain pharmacological or biological activity has properties that would make it a likely orally active drug in humans. This is because amantadine and rimantadine possesses very few pharmacophore groups and very few hydrogen-bond-forming elements. Rimantadine can hold one of the four helices in the tetrameric M2 proton channel by one, and only one, pharmacophore amino group. An additional pharmacophore group is needed to hold the adjacent helix of the tetrameric channel so as to strengthen its closed conformation for blocking the proton conductance. The high-resolution NMR structure of the M2 proton channel and the gating and inhibiting mechanism revealed therefrom has made it possible to rationally design new and more powerful drugs against influenza viruses. It is the second pharmacophore group in the inhibitors A4 and A5 that might significantly enhance their ability in inhibiting the M2 channel in comparison with amantadine and rimantadine. The M2 proton channel is a membrane protein; while the adamantane-based inhibitors are detergent-like compounds with a hydrophilic head and a hydrophobic body, possessing the ability to penetrate the bilayer lipid membrane. Although the second additional hydrophilic pharmacophore group of A4 and A5 inhibitors can enhance their inhibition ability to the M2 proton channel, it might lower their ability in penetrating membrane. Therefore, a series of follow-up experiments are needed along this direction to find an optimal inhibitor by taking into account these two aspects. In the last decade, the inhibition of protein-protein interactions has emerged from both academic and private research as a new way to modulate the activity of proteins. Based on this new focus, it is now more and more commonly accepted that protein-protein complexes are an important class of therapeutic targets. PPIs can be involved in a network of complex interactions that play a central role in various cellular events. These interactions control processes involved in both normal and pathological pathways, which include signal transduction, cell adhesion, cellular proliferation, growth, differentiation, viral self-assembly, programmed cell death and cytoskeleton structure.