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

Research output: Contribution to journal › Article › peer-review

43 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 (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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Molecular Medicine
Drug Discovery

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10.1021/jm060872x

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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.",

author = "Harki, \{Daniel A.\} and Graci, \{Jason D.\} and Galarraga, \{Jessica E.\} and Chain, \{William J.\} and Cameron, \{Craig E.\} and Peterson, \{Blake R.\}",

year = "2006",

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doi = "10.1021/jm060872x",

language = "English (US)",

volume = "49",

pages = "6166--6169",

journal = "Journal of Medicinal Chemistry",

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TY - JOUR

T1 - Synthesis and antiviral activity of 5-substituted cytidine analogues

T2 - Identification of a potent inhibitor of viral RNA-dependent RNA polymerases

AU - Harki, Daniel A.

AU - Graci, Jason D.

AU - Galarraga, Jessica E.

AU - Chain, William J.

AU - Cameron, Craig E.

AU - Peterson, Blake R.

PY - 2006/10

Y1 - 2006/10

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AB - 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.

UR - https://www.scopus.com/pages/publications/33750111990

UR - https://www.scopus.com/pages/publications/33750111990#tab=citedBy

U2 - 10.1021/jm060872x

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SN - 0022-2623

VL - 49

SP - 6166

EP - 6169

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 21

ER -

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

Abstract

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