ANTIHERPESVIRUS ACTIVITIES OF (1'S,2'R)-9-([1',2'-BIS(HYDROXYMETHYL) CYCLOPROP-1'-YL]METHYL)GUANINE (A-5021) IN CELL-CULTURE

Antiherpetic activity of (1'S,2'R)-9-{[1 ',2'-bis (hydroxymethyl) cycl oprop-1'-yl] methyl)guanine (A-5021) was compared with those of acyclo vir (ACV) and penciclovir (PCV) in cell cultures. In a plaque reductio n assay using a selection of human cells, A-5021 showed the most poten t activity in all cells. Against clinical isolates of herpes simplex v irus type 1 (HSV-1, n = 5) and type 2 (HSV-2, n = 6), mean 50% inhibit ory concentrations (IC(50)s) for A-5021 were 0.013 and 0.15 mu g/ml, r espectively, in MRC-5 cells. Corresponding IC(50)s for ACV were 0.22 a nd 0.30 mu g/ml, and those for PCV were 0.84 and 1.5 mu g/ml, respecti vely. Against clinical isolates of varicella-zoster virus (VZV, n = 5) , mean IC(50)s for A-5021, ACV, and PCV were 0.77, 5.2, and 14 mu g/ml , respectively, in human embryonic lung (HEL) cells. A-5021 showed con siderably more prolonged antiviral activity than ACV when infected cel ls were treated for a short time. The selectivity index, the ratio of 50% cytotoxic concentration to IC50, of A-5021 was superior to those o f ACV and PCV for HSV-1 and almost comparable for HSV-2 and VZV. In a growth inhibition assay of murine granulocyte-macrophage progenitor ce lls, A-5021 showed the least inhibitory effect of the three compounds. These results show that A-5021 is a potent and selective antiviral ag ent against HSV-1, HSV-2, and VZV.