Inhibition of Influenza A and B Viruses by 2′-Deoxy-2′-Fluororibosides
| Autor: | K. L. Powell, Margaret Tisdale, G. Darby, G. Appleyard, D. J. Nelson, D. J. M. Purifoy, W. Al Nakib, J. N. Stables, J. V. Tuttle, S. Nusinoff-Lehrman |
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| Rok vydání: | 1993 |
| Předmět: |
0301 basic medicine
Chemotherapy Ratón Influenzavirus B medicine.medical_treatment 030106 microbiology Orthomyxoviridae General Medicine Biology medicine.disease biology.organism_classification 01 natural sciences Virology Virus 0104 chemical sciences 010404 medicinal & biomolecular chemistry 03 medical and health sciences Pneumonia medicine.anatomical_structure medicine Viral disease Fibroblast |
| Zdroj: | Antiviral Chemistry and Chemotherapy. 4:281-287 |
| ISSN: | 2040-2066 |
| Popis: | A series of 2′-deoxy-2′-fluororibosides were evaluated for anti-influenza activity in cell culture and in the mouse pneumonia model. Many were found to be potent inhibitors of Influenza A, in chick embryo fibroblast cells (IC50's 0.1–2.9 μM), and in reducing mouse lung virus titres (1–3 log10units).Purine analogues proved the most effective, but their activity was an order of magnitude higher in MDCK cells. Anti-influenza activity correlated with intracellular triphosphate levels and with substrate specificity of 2′-deoxycytidine kinase. 2′-deoxy-2′-fluoroguanosine selected for further study was active against all influenza A and B strains tested, including one clinical isolate which proved extremely sensitive when assayed in human tracheal cultures. In vivo, 2′-deoxy-2′-fluoroguanosine (2′-fluorodGuo) was significantly more effective than amantadine or ribavirin in reducing mouse lung virus titre when treatment commenced after infection. |
| Databáze: | OpenAIRE |
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