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Antiviral Activity and Mechanism of Action of Ganciclovir

Thomas Matthews and Richard Boehme
Reviews of Infectious Diseases
Vol. 10, Supplement 3. Cytomegalovirus Infection and Treatment with Ganciclovir (Jul. - Aug., 1988), pp. S490-S494
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/4454628
Page Count: 5
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Antiviral Activity and Mechanism of Action of Ganciclovir
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Abstract

Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) is a potent inhibitor of viruses of the herpes family, including cytomegalovirus (CMV), that are pathogenic for humans and animals. The primary mechanism of ganciclovir action against CMV is inhibition of the replication of viral DNA by ganciclovir-5'-triphosphate (ganciclovir-TP). This inhibition includes a selective and potent inhibition of the viral DNA polymerase. Ganciclovir is metabolized to the triphosphate form by primarily three cellular enzymes: (1) a deoxyguanosine kinase induced by CMV-infected cells; (2) guanylate kinase; and (3) phosphoglycerate kinase. Other nucleotide-metabolizing enzymes may be involved as well. The selective antiviral response associated with ganciclovir treatment is achieved because of the much weaker inhibition of cellular DNA polymerases by ganciclovir-TP. Activity and selectivity are also amplified by the accumulation of ganciclovir-TP in CMV-infected cells.

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