Antiviral activity of 2'-deoxy-2'-fluoro-β-D-arabinofuranosyl-5-iodocytosine against human cytomegalovirus in human skin fibroblasts Journal Article
| Authors: | Colacino, J. M.; Lopez, C. |
| Article Title: | Antiviral activity of 2'-deoxy-2'-fluoro-β-D-arabinofuranosyl-5-iodocytosine against human cytomegalovirus in human skin fibroblasts |
| Abstract: | 2'-Deoxy-2'-fluoro-β-D-arabinofuranosyl-5-iodocytosine (FIAC) was shown to be a selective anti-human cytomegalovirus agent in vitro with a 50% antiviral effective dose of 0.6 μM (J.M. Colacino and C. Lopez, Antimicrob. Agents Chemother. 26:505-508, 1983) and a 50% cell growth inhibitory dose of 8 μM. Antiviral activity was more readily reversed with 10-fold excess thymidine, whereby the 50% effective dose was increased to 11.3 μM. FIAC-induced cytotoxicity was more readily reversed with 10-fold excess of deoxycytidine, whereby the 50% inhibitory dose was increased to greater than 100 μM. Thymidine was unable to reverse completely the antiviral activity of FIAC. Although the extent of phosphorylation of thymidine, deoxycytidine, and deoxyuridine was 6-, 4-, and 4-fold greater, respectively, in human cytomegalovirus-infected cell lysates than in uninfected cell lysates, the extent of phosphorylation of FIAC was only 1.3-fold greater in human cytomegalovirus-infected cell lysates than in uninfected cell lysates. By comparison, the extent of FIAC phosphorylation was 500 times greater in herpes simplex virus type 1-infected cells than in uninfected cell lysates. Methotrexate was 400 times more effective against human cytomegalovirus replication than it was against herpes simplex virus type 1 replication, indicating that thymidylate synthetase may be important for human cytomegalovirus replication. However, 10 μM FIAC did not inhibit thymidylate synthetase activity in uninfected or virus-infected cells as determined by their metabolism of [6-3H]deoxyuridine in the presence or absence of drug. FIAC at 1 μM suppresses and FIAC at 10 μM completely inhibits human cytomegalovirus DNA replication as indicated by Southern blot analysis. This inhibition was reversible. FIAC incorporation into the DNA of human cytomegalovirus strain AD169-infected cells was stimulated relative to that in nondividing, uninfected cells. |
| Keywords: | unclassified drug; human cell; drug efficacy; nucleoside analog; in vitro study; cell culture; antivirus agent; virus infection; radioisotope; virus replication; skin fibroblast; human cytomegalovirus; fiacitabine; human; priority journal; article; deoxyuridine h 3 |
| Journal Title: | Antimicrobial Agents and Chemotherapy |
| Volume: | 28 |
| Issue: | 2 |
| ISSN: | 0066-4804 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1985-08-01 |
| Start Page: | 252 |
| End Page: | 258 |
| Language: | English |
| DOI: | 10.1128/aac.28.2.252 |
| PUBMED: | 3010842 |
| PROVIDER: | scopus |
| PMCID: | PMC180228 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
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