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

doi:10.1021/jm060872x

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

Medicinal Chemistry

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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 μM), and this inhibition is sufficient to explain the observed antiviral activity.

Original language	English (US)
Pages (from-to)	6166-6169
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	49
Issue number	21
DOIs	https://doi.org/10.1021/jm060872x
State	Published - Oct 2006

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

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AU - Chain, William J.

AU - Cameron, Craig E.

AU - Peterson, Blake R.

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

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