The potency of acyclovir can be markedly different in different cell types

Acyclovir is an acyclic guanine analog with a considerable activity against herpes simplex viruses. We studied the antiherpetic activity of acyclovir in macrophages and fibroblast cell lines. Utilising a plaque reduction assa y we found that acyclovir potently inhibited the HSV-1 replication in macro phages (EC50 = 0.0025 muM) compared to Vero (EC50 = 8.5 muM) and MRC-5 (EC5 0 = 3.3 muM) cells. The cytotoxicity of acyclovir was not detected at conce ntrations less than or equal to 20 muM, thus the selective index in macroph ages was >8000. This marked difference in antiherpetic activity between mac rophages and fibroblasts was not observed with Foscarnet and PMEA. We sugge st that this potent antiviral effect of acyclovir is mainly due to a profic ient phosphorylation of the drug and/or a favourable dGTP/acyclovir triphos phate ratio in macrophage cells. (C) 2001 Elsevier Science Inc. All rights reserved.