Virus replication inhibitory peptide inhibits the conversion of phospholipid bilayers to the hexagonal phase

Virus replication inhibitory peptide (carbobenzoxy-D-Phe-L-PheGly) was shown to be a potent specific inhibitor of the replication of paramyxovirus and myxovirus (Richardson, Scheid and Choppin (1980), Virology105, 205–222). This peptide inhibits the membrane fusing activity of a viral glycoprotein.Many agents which promote the formation of the hexagonal phase in membranes also accelerate membrane fusion. At a mole fraction of 0.1, viral replication inhibitory peptide can raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine by almost 10°. Two related peptides, carbobenzoxy-L-PheGly and carbobenzoxy-L-GlyPhe, are less potent in raising the bilayer to hexagonal phase transition temperature, with the latter peptide being the least effective of the three. This order of potency is the same as the order of potency in inhibiting viral replication. Substances which inhibit hexagonal phase formation of pure lipids may also inhibit membrane fusion.Abbreviations DEPE dielaidoylphosphatidyethanolamine - Z carbobenzoxy - DSC differential scanning calorimetry - VRIP virus replication inhibitory peptide (Z-D-Phe-L-PheGly)