Elsevier

Virus Research

Volume 107, Issue 2, February 2005, Pages 141-149
Virus Research

Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective

https://doi.org/10.1016/j.virusres.2004.11.004Get rights and content

Abstract

Positive-strand RNA viruses exist as a quasi-species due to the incorporation of mutations into the viral genome during replication by the virus-encoded RNA-dependent RNA polymerase (RdRP). Therefore, the RdRP is often described as a low-fidelity enzyme. However, until recently, a complete description of the kinetic, thermodynamic and structural basis for the nucleotide incorporation fidelity of the RdRP has not been available. In this article, we review the following: (i) the steps employed by the RdRP to incorporate a correct nucleotide; (ii) the steps that are employed by the RdRP for nucleotide selection; (iii) the structure-based hypothesis for nucleotide selection; (iv) the impact of sites remote from the active site on polymerase fidelity. Given the recent observation that RNA viruses exist on the threshold of error catastrophe, the studies reviewed herein suggest novel strategies to perturb RdRP fidelity that may lead ultimately to the development of antiviral agents to treat RNA virus infection.

Keywords

Polymerase fidelity
RdRP
Nucleotide selection

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This work was supported, in part, by a grant (AI45818) from the NIAID, National Institutes of Health. C.E.C. is the recipient of an established investigator award (0340028N) from the American Heart Association.

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