Journal
ANTIVIRAL RESEARCH
Volume 47, Issue 2, Pages 111-120Publisher
ELSEVIER
DOI: 10.1016/S0166-3542(00)00096-6
Keywords
cytomegalovirus; thymidylate synthase; antifolate; ZD1694; ganciclovir
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Tomudex (ZD1694) is a quinazoline-based folate analog and a powerful inhibitor of cellular thymidylate synthase and is approved in Europe for use in oncology. Here the first evidence of its activity against murine and human cytomegalovirus (MCMV and HCMV) is reported. ZD1694 irreversibly inhibited the replication and DNA synthesis of both viruses in quiescent fibroblasts. The corresponding 50% effective concentrations were 0.006 and 0.002 mu M respectively, whereas the 50% cytotoxic concentration was >10 mu M for both murine and human quiescent fibroblasts. A similar antiviral effect was observed against two ganciclovir-resistant HCMV strains isolated from AIDS patients. Taken as a whole these results demonstrate that cellular thymidylate synthase plays an essential role in viral replication and that ZD1693 merits further investigation as anticytomegaloviral agent. (C) 2000 Published by Elsevier Science B.V.
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