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Antiherpetic activity of (1′S ,2′R )-9-{[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine (A-5021) was compared with those of acyclovir (ACV) and penciclovir (PCV) in cell cultures. In a plaque reduction assay using a selection of human cells, A-5021 showed the most potent activity in all cells. Against clinical isolates of herpes simplex virus type 1 (HSV-1,n = 5) and type 2 (HSV-2,n = 6), mean 50% inhibitory concentrations (IC50 s) for A-5021 were 0.013 and 0.15 μg/ml, respectively, in MRC-5 cells. Corresponding IC50 s for ACV were 0.22 and 0.30 μg/ml, and those for PCV were 0.84 and 1.5 μg/ml, respectively. Against clinical isolates of varicella-zoster virus (VZV,n = 5), mean IC50 s for A-5021, ACV, and PCV were 0.77, 5.2, and 14 μg/ml, respectively, in human embryonic lung (HEL) cells. A-5021 showed considerably more prolonged antiviral activity than ACV when infected cells were treated for a short time. The selectivity index, the ratio of 50% cytotoxic concentration to IC50 , of A-5021 was superior to those of ACV and PCV for HSV-1 and almost comparable for HSV-2 and VZV. In a growth inhibition assay of murine granulocyte-macrophage progenitor cells, A-5021 showed the least inhibitory effect of the three compounds. These results show that A-5021 is a potent and selective antiviral agent against HSV-1, HSV-2, and VZV.

Antiherpesvirus Activities of (1′ S ,2′ R )-9-{[1′,2′-Bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine (A-5021) in Cell Culture