Increased Efficacy of Zinc Complexes With Picolinic and Aspartic Acids Against Herpes Simplex Virus (HSV) Infection When Combined With the Pavine Alkaloid (-)-Thalimonine

Complexes of zinc with picolinic and aspartic acids inhibit key steps of HSV-1 replication affecting different virus-specific targets. As was recently demonstrated by us, the pavine alkaloid (-)-thalimonine irreversibly inhibits HSV-1 infection in cultured cells. The aim of the present study was the evaluation of the combined effect of zinc complexes and (-)-thalimonine on uninfected and HSV-1 infected cells. The data obtained have shown that zinc complexes and the alkaloid exert decreased cytotoxicity (antagonistic effect) and significantly increased anti-HSV-1 activity (synergistic effect) when applied in dual chess-board combinations as compared to the individual effects of compounds tested. These combinations are also effective against the infection caused by a resistant to acyclovir (ACV) HSV-1 mutant and the effect has been recognised as synergistic.