We have found that when copper, zinc or cobalt is bound to a suitable ligand, the
appropriate complex exhibited a significant anti-HSV effect (Varadinova et al., 1993; 1996).
Recently published data by Sagripanti et al. (1997) also show that the inhibition of HSV by
copper was enhanced by reducing agents and that mechanism of the inactivation is similar
as for copper-mediated DNA damage (Aruoma, et al. 1991; Dizdaroglu, et al., 1991;
Toyokuni and Sagripanti, 1994). Therefore it was interesting to study the efect of Cu(ll)
coordination compounds with acyclovir (ACV) on the replication of HSV in cultured cells.
The experiments on cytotoxicity as well as on the activity of three different Cu-ACV
complexes [Cu(ACV)2Cl2(H2O)2] = (A); [Cu(ACV)2(H2O)3](NO3)2.H2O = (B) and
[Cu(ACV)2(H2O)2](NO3)2] = (C) towards virus replication, with special attention on the growth of
ACV-resistant strain R-100 were performed on MDBK cells. ACV was used as a reference
compound. The following results were obtained: 1) Increased cell’s viability in the presence
of 20-40(g/ml ACV and decreased one in the presence of Cu-ACV complexes with relative
level (A) >> (B) > (C); 2) Cu-ACV complexes are more cytotoxic than the ligand - ACV and the
relative level is (C)>(B)>(A); 3) The anti-HSV effect of ACV can be modulated by copper at
levels depending on the specificity of the particular virus strain: (i) for the ACV sensitive strain
DA (HSV-1) - ACV ((A) > (C) > (B); (ii) for the ACV sensitive strain Bja (HSV-2) (A) > ACV > (C) > (B); (iii) for strain R-100 ( ACVR, TKa) - (A) > ACV > (C) > (B). This findings are consistent with
previously published data and undoubtedly show that Cu-ACV complexes could be useful in
the treatment of HSV infections, especially when the causative agent is a resistant to ACV
mutant.
