| 摘要 |
The present invention provides, among other things, methods for the identification of compounds that are capable of modulating the activity of the influenza A virus. For example, the present methods provide platforms for identifying small molecule inhibitors that target the proton transport pathway defined at least in part by two or more of the highly conserved channel residues 27, 30, 31, 34, 37, 41, 44, and 45 of the influenza A M2 protein. In one aspect, the present invention is directed to methods comprising comparing spatial models of a plurality of test compounds with the spatial model of the pathway defined by at least two residues from among residues 27, 30, 31, 34, 37 or 41, 44, and 45 on one or more subunits of the M2 transmembrane protein of the influenza A virus to determine the spatial complementarity of each of the test compounds with the pathway; assessing the ability of the test compounds to bind to the pathway; and, based on the assessed ability of the test compounds to bind the pathway, determining the compound that modulates the activity of influenza A.
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