Synthesis and antiviral activity of 5-substituted cytidine analogues: Identification of a potent inhibitor of viral RNA-dependent RNA polymerases

Daniel A. Harki, Jason D. Graci, Jessica E. Galarraga, William J. Chain, Craig E. Cameron, Blake R. Peterson

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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 (Kd = 1.1 ± 0.1 μM), and this inhibition is sufficient to explain the observed antiviral activity.

Original languageEnglish (US)
Pages (from-to)6166-6169
Number of pages4
JournalJournal of medicinal chemistry
Volume49
Issue number21
DOIs
StatePublished - Oct 2006

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