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 journalArticle

31 Citations (Scopus)

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 1 2006

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RNA Replicase
Cytidine
Poliovirus
Viral RNA
Antiviral Agents
Enterovirus
Ribavirin
Mutagens
Mutagenesis
Pharmaceutical Preparations
5-nitrocytidine
triphosphoric acid

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Harki, Daniel A. ; Graci, Jason D. ; Galarraga, Jessica E. ; Chain, William J. ; Cameron, Craig E. ; Peterson, Blake R. / Synthesis and antiviral activity of 5-substituted cytidine analogues : Identification of a potent inhibitor of viral RNA-dependent RNA polymerases. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 21. pp. 6166-6169.
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Synthesis and antiviral activity of 5-substituted cytidine analogues : Identification of a potent inhibitor of viral RNA-dependent RNA polymerases. / Harki, Daniel A.; Graci, Jason D.; Galarraga, Jessica E.; Chain, William J.; Cameron, Craig E.; Peterson, Blake R.

In: Journal of Medicinal Chemistry, Vol. 49, No. 21, 01.10.2006, p. 6166-6169.

Research output: Contribution to journalArticle

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