title: Synthesis and antiviral activity of 5-substituted cytidine analogues: identification of a potent inhibitor of viral RNA-dependent RNA polymerases.
abstract: As part of our studies of lethal viral mutagens, a series of 5-substituted cytidine analogues were synthesized and evaluated for antiviral activity. Among the compounds examined, 5-nitrocytidine was effective against poliovirus (PV) and coxsackievirus B3 (CVB3) and exhibited greater activity than the clinically employed drug ribavirin. Instead of promoting viral mutagenesis, 5-nitrocytidine triphosphate inhibited PV RNA-dependent RNA polymerase (K(d) = 1.1 +/- 0.1 microM), and this inhibition is sufficient to explain the observed antiviral activity.
authors.affiliation: Department of Chemistry and Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Harki
authors.forename: Jason D
authors.initials: JD
authors.lastname: Graci
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Galarraga
authors.forename: William J
authors.initials: WJ
authors.lastname: Chain
authors.forename: Craig E
authors.initials: CE
authors.lastname: Cameron
authors.forename: Blake R
authors.initials: BR
authors.lastname: Peterson
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D029822:Enterovirus B, Human / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D017955:Poliovirus / Q000187:drug effects / Q000201:enzymology; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C515132:5-nitrocytidine; D000998:Antiviral Agents; D003562:Cytidine; D012324:RNA-Dependent RNA Polymerase