An amphipathic alpha-helical synthetic peptide analogue of melittin inhibits herpes simplex virus-1 (HSV-1)-induced cell fusion and virus spread

The effects of hecate, a 23-amino acid synthetic peptide analogue of melittin, on HSV-1-induced cell fusion and virus multiplication was investigated. Hecate completely inhibited cell fusion induced by HSV-1 syncytial (syn) mutants HSV-1 HFEM (tsB5) and HSV-1 mp (MP) at a concentration of 5.0 microM. Metabolic labeling experiments indicated that hecate did not adversely affect cellular growth and protein synthesis. The synthesis of virus-specified glycoproteins B, C, D, and H was reduced in the presence of hecate; however, the transport of these glycoproteins to the surface of infected cells was not affected. Production of infectious virions for wild-type and syn mutants tsB5 and MP was reduced in the presence of hecate. The effect of hecate on virus titer was dependent on the multiplicity of infection. Virus titers were reduced 2-28-fold at an M.O.I. of 0.1, 3-6-fold at an M.O.I. of 0.5, and 0-2.5-fold at an M.O.I. of 2.5. Direct treatment of semipurified virions with hecate reduced titers by approximately 4-fold for KOS, 2-fold for tsB5, and over 30-fold for MP.