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Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level

Item Type:Article
Title:Inhibition of adenovirus DNA polymerase by modified nucleoside triphosphate analogs correlate with their antiviral effects on cellular level
Creators Name:Mentel, R. and Kurek, S. and Wegner, U. and von Janta-Lipinski, M. and Gurtler, L. and Matthes, E.
Abstract: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 (IC 50 0.63 μM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC 50 0.71 μM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC 50 2.96 μM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC 50 1.0 μM), 2',3'-dideoxyadenosine triphosphate (IC 50 1.6 μM) and 2',3'-dideoxythymidine triphosphate (IC 50 1.82 μM). 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.
Keywords:Antiviral Activity, Human Adenovirus, L-Enantiomers, Modified Nucleoside Analogs, Polymerase, Animals
Source:Medical Microbiology and Immunology
ISSN:0300-8584
Publisher:Springer-Verlag (Germany)
Volume:189
Number:2
Page Range:91-95
Date:1 November 2000
Official Publication:https://doi.org/10.1007/s004300000046
PubMed:View item in PubMed

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