Joseph Moulton, Brigham Young University
Physiology and Developmental Biology
With the advent of recent mutations in the influenza A viral genome, drugs that previously blocked the proton flux responsible for disassembly of the viral envelope and exposure of viral RNA to the transcriptional machinery of the host cell have become ineffective. Our study of the M2 hydrogen ion channel responsible for this flux has led to a vastly-increased under- standing of the mechanisms behind the conductance activity and potential blockage of these transmembrane tetramers. By embedding M2 proton channel subunits of the S31N mutant strain into liposomal bilayers and suspending these bilayers in the buffers and ionic gradients characteristic of the intracellular environment, we have been able to simulate and observe nor- mal functioning of the influenza A virus. Using these liposomal bilayers, we have developed a series of experimental protocols to test a variety of amantadine- and rimantadine-related drugs for successful blockage of M2 S31N proton conductance. Our research presentation will be centered around the mechanisms of this channel and the favorable results that we have obtained from many of these drugs.