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Therapeutically targeting RNA viruses via lethal mutagenesis

    Jason D Graci

    PTC Therapeutics, Inc., 100 Corporate Court, South Plainfield, NJ 07080, USA.

    &
    Craig E Cameron

    † Author for correspondence

    The Pennsylvania State University, Department of Biochemistry & Molecular Biology, 201 Althouse Laboratory, University Park, PA 16802, USA.

    Published Online:https://doi.org/10.2217/17460794.3.6.553

    RNA viruses exhibit increased mutation frequencies relative to other organisms. Recent work has attempted to exploit this unique feature by increasing the viral mutation frequency beyond an extinction threshold, an antiviral strategy known as lethal mutagenesis. A number of novel nucleoside analogs have been designed around this premise. Herein, we review the quasispecies nature of RNA viruses and survey the antiviral, biological and biochemical characteristics of mutagenic nucleoside analogs, including clinically-used ribavirin. Biological implications of modulating viral replication fidelity are discussed in the context of translating lethal mutagenesis into a clinically-useful antiviral strategy.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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