Abstract
Acyclovir, 9-(2-hydroxyethoxymethyl)guanine, is an acyclic nucleoside analogue which has a high activity and selectivity for herpes viruses, particularly herpes simplex viruses types 1 and 2 and varicella zoster virus. This selectivity is due to the initial activation of the drug by phosphorylation by a herpes virus-specified thymidine kinase. Normal cellular enzymes do not phosphorylate acyclovir to any significant degree. Acyclovir monophosphate is subsequently converted to a triphosphate which is a more potent inhibitor of herpes virus DNA polymerases than of cellular DNA polymerases. The relationship between the amount of acyclovir triphosphate formed and its inhibition constant (Ki) for the particular viral or cellular DNA polymerase is predictive of the inhibitory activity of acyclovir on DNA replication.
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