The biochemistry and mechanism of action of acyclovir

GB Elion - Journal of Antimicrobial Chemotherapy, 1983 - academic.oup.com
GB Elion
Journal of Antimicrobial Chemotherapy, 1983academic.oup.com
Abstract Acydovir, 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 …
Abstract
Acydovir, 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 inhbitory activity of acyclovir on DNA replication.
Oxford University Press