INHIBITION OF INFLUENZA-A AND INFLUENZA-B VIRUSES BY 2'-DEOXY-2'-FLUORORIBOSIDES

被引:34
作者
TISDALE, M
APPLEYARD, G
TUTTLE, JV
NELSON, DJ
NUSINOFFLEHRMAN, S
ALNAKIB, W
STABLES, JN
PURIFOY, DJM
POWELL, KL
DARBY, G
机构
[1] BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709
[2] ADV PATHOL SERV,LONDON,ENGLAND
关键词
D O I
10.1177/095632029300400504
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 muM), and in reducing mouse lung virus litres (1-3 log10 units). 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.
引用
收藏
页码:281 / 287
页数:7
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