Entryof enveloped viruses requires fusion of viral and cellularmembranes, driven by conformational changes of viral glycoproteins.The crystallized trimeric glycoprotein gB of herpes simplex virushas been described as a postfusion conformation, and several studiesprove that like other class III fusion proteins, gB undergoes a pH-dependentswitch between the pre- and postfusion conformations. Using severalbiophysical techniques, we show that peptides corresponding to thelong helix of the gB postfusion structure interfere with the membranefusion event, likely hampering the conformational rearrangements fromthe pre- to the postfusion structures. Those peptides represent goodcandidates for further design of peptidomimetic antagonists capableof blocking the fusion process. [ABSTRACT FROM AUTHOR]