Baseline data.

<p>The P values with “*”were obtained using Fisher’s Exact Test, whereas the rest were the result of independent samples t-test.</p

Localization of the acupuncture specific effects by comparing TE5 verum acupuncture (Group A) vs. TE5 sham acupuncture (Group B) and TE5 verum acupuncture (Group A) vs. nonacupoint acupuncture (Group C).

<p>Abbreviation: BA, Brodmann area; Vox, voxel (represents the number of voxels); N/A, not available (means that the peak voxel was out of the BA zone). The BA area marked by “*”was corrected by a neurological physician.</p

Consort flow diagram.

<p>Consort flow diagram.</p

Stimulation and scanning pattern.

<p>Stimulation and scanning pattern.</p

Differences of seed associated networks between ROIs from the left hemisphere and the right hemisphere.

<p>Full line represents stronger correlation under acupuncture compared with sham acupuncture, whereas the “dash–dot–dot” line represents weaker correlation. Dash line stands for weaker correlation compared with nonacupoint acupuncture (P<0.05, multiple comparison error corrected using Monte Carlo simulation). Regions of the left hemisphere and right hemisphere that had significant differences in correlation with seeds are placed on left side and right side, respectively, and ROIs in the same box are from the same hemisphere.</p

Discovery of Novel Dual Inhibitors of the Wild-Type and the Most Prevalent Drug-Resistant Mutant, S31N, of the M2 Proton Channel from Influenza A Virus

Anti-influenza drugs, amantadine and rimantadine, targeting the M2 channel from influenza A virus are no longer effective because of widespread drug resistance. S31N is the predominant and amantadine-resistant M2 mutant, present in almost all of the circulating influenza A strains as well as in the pandemic 2009 H1N1 and the highly pathogenic H5N1 flu strains. Thus, there is an urgent need to develop second-generation M2 inhibitors targeting the S31N mutant. However, the S31N mutant presents a huge challenge to drug discovery, and it has been considered undruggable for several decades. Using structural information, classical medicinal chemistry approaches, and M2-specific biological testing, we discovered benzyl-substituted amantadine derivatives with activity against both S31N and WT, among which 4-(adamantan-1-ylaminomethyl)-benzene-1,3-diol (<b>44</b>) is the most potent dual inhibitor. These inhibitors demonstrate that S31N is a druggable target and provide a new starting point to design novel M2 inhibitors that address the problem of drug-resistant influenza A infections