Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level
| Autor: | Eckart Matthes, Stefan Kurek, Renate Mentel, Martin von Janta-Lipinski, Lutz Gürtler, Ursula Wegner |
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| Rok vydání: | 2000 |
| Předmět: |
Microbiology (medical)
DNA polymerase Immunology DNA-Directed DNA Polymerase Microbial Sensitivity Tests medicine.disease_cause Antiviral Agents Cell Line chemistry.chemical_compound medicine Animals Immunology and Allergy Enzyme Inhibitors Polymerase Nucleic Acid Synthesis Inhibitors chemistry.chemical_classification biology Nucleotides Adenoviruses Human Stereoisomerism General Medicine Nucleotidyltransferase Virology Molecular biology Nucleoside-diphosphate kinase Adenoviridae Enzyme chemistry Deoxycytosine Nucleotides biology.protein Nucleoside triphosphate Nucleoside Dideoxynucleotides |
| Zdroj: | Medical Microbiology and Immunology. 189:91-95 |
| ISSN: | 1432-1831 0300-8584 |
| DOI: | 10.1007/s004300000046 |
| Popis: | Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3'-fluorothymidine triphosphate (IC50 0.63 microM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC50 0.71 microM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC50 2.96 microM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC50 1.0 microM), 2',3'-dideoxyadenosine triphosphate (IC50 1.6 microM) and 2',3'-dideoxythymidine triphosphate (IC50 1.82 microM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3'-fluorothymidine and 2',3'-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity. |
| Databáze: | OpenAIRE |
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