Influenza antivirals based on membrane fusion inhibition are widely used in Asia, but are currently disregarded in Occident. Understanding the influenza fusion peptide membrane fusion mechanism is necessary to get approval for such antivirals. We studied the effect of the influenza fusion peptide on surrounding membrane phospholipids at the atomic level using extensive molecular dynamics simulations. We observed a specific interaction between the fusion peptide and phospholipids that could explain membrane fusion catalysis in a comprehensive way. The interaction occurs between the peptide N-terminal amines and the lipid phosphate group. It induces both lipid tail protrusion and polar head intrusion in the membrane. Those lipid perturbations would decrease repulsive electrostatic, hydration and fluctuation forces between membranes to allow fusion. Such simple membrane fusion mechanism may be common among the fusogenic tilted peptides. Molecules interfering with the observed fusion peptide-phospholipid interaction represent a new influenza antiviral target.

Influenza fusion peptides prime lipids for membrane fusion using specific interactions

245th National Meeting (2013)

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