1995
DOI: 10.1128/aac.39.11.2454
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Inhibition of influenza virus transcription by 2'-deoxy-2'-fluoroguanosine

Abstract: The nucleoside analog 2-deoxy-2-fluoroguanosine (2-fluorodGuo) is phosphorylated by cellular enzymes and reversibly inhibits influenza virus replication in chick embryo cells within the first 4 h of infection. RNA hybridization studies revealed that primary and secondary transcription of influenza virus RNA were blocked at a compound concentration of 10 M, but no inhibition of cell protein synthesis was seen even at high compound concentrations (200 M). In vitro, the triphosphate of 2-fluorodGuo is a competiti… Show more

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Cited by 58 publications
(46 citation statements)
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“…2Ј-Deoxy-2Ј-␣-fluorocytidine triphosphate was shown to be a potent inhibitor of NS5B (25). However, this and other nucleosides carrying the 2Ј-deoxy-2Ј-␣-fluoro moiety are known to have limited selectivity and can be substrates and chain-terminating inhibitors of viral and human polymerases (25,26). Therefore, 2Ј-␣-fluoro-nucleosides are unlikely to become useful drugs for the treatment of HCV infection due to a lack of polymerase selectivity.…”
Section: Discussionmentioning
confidence: 99%
“…2Ј-Deoxy-2Ј-␣-fluorocytidine triphosphate was shown to be a potent inhibitor of NS5B (25). However, this and other nucleosides carrying the 2Ј-deoxy-2Ј-␣-fluoro moiety are known to have limited selectivity and can be substrates and chain-terminating inhibitors of viral and human polymerases (25,26). Therefore, 2Ј-␣-fluoro-nucleosides are unlikely to become useful drugs for the treatment of HCV infection due to a lack of polymerase selectivity.…”
Section: Discussionmentioning
confidence: 99%
“…Influenza virus RNA synthesis takes place within the nucleus of infected cells, consistent with the requirement for host cell pre-mRNAs and for splicing (26), suggesting that influenza virus transcription may be coupled to host cell RNA polymerase II transcription (14). Inhibitors selective for either influenza virus endonuclease or RNA polymerase activities suggest that the active site for endonuclease cleavage is separate from the transcription active site (50,51).…”
mentioning
confidence: 92%
“…Cap 0 mRNAs are approximately 10% as effective in priming as cap 1-containing globin mRNAs, however, indicating that the presence of a 2Ј-O-methyl group is important in priming influenza virus mRNA (4,5). The endonuclease and polymerase activities show differences in metal ion preference (10), and inhibitors selective for either endonuclease or polymerase activities are known (39,40), showing that the endonuclease active site is separate from that of the polymerase. Cap structures are known to cross-link specifically to the PB2 subunit of the RNA polymerase complex (41), suggesting that the PB2 subunit catalyzes endonuclease activity, although all three polymerase subunits (PB1, PB2, and PA) appear to be required for activity (3,36).…”
mentioning
confidence: 99%