Antiviral activity of meliacine on the replication of a thymidine kinase-deficient mutant of Herpes simplex virus type 1 alone and in combination with acyclovir

The anti-HSV-l activity of meliacine (MA), a peptide isolated from leaves of Melia azedarach L,., alone and in combination with acyclovir (ACV), was assayed against thymidine kinase-deficient (TK-) Virus yields in vitro. MA alone proved to inhibit significantly TK- viral replication, whereas ACV was more potent than MA as an inhibitor of TK+ replication. TK- and TK+ synergistic inhibition by the combination of both agents was observed at concentrations that did not alter cell viability. The interaction between MA and ACV was quantitatively determined by calculating the combination index and plotting the data by the isobologram method. Besides, MA and ACV were able to suppress synergistically the antigen expression on HSV-I infected cells processed by an immunofluorescence assay. These in vitro findings suggest that combinations of MA and ACV at appropriate doses may provide an increased efficacy in inhibiting both TK- and TK+ HSV-1 multiplication. (C) 1997 Elsevier Science B.V.