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Specific inhibition of herpesvirus ribonucleotide reductase by synthetic peptides

Naturevolume 321pages439441 (1986) | Download Citation



Ribonucleotide reductase is an essential enzyme for DNA synthesis in all prokaryotic and eukaryotic cells; it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. Several herpesviruses including herpes simplex virus type 1 (HSV-1)1, HSV-22, pseudorabies virus (PRV)3, equine herpesvirus type 1 (EHV-1)4 and Epstein–Barr virus (EBV)5 have been found to induce novel ribonucleotide reductase activities. There is evidence that the HSV-1 ribonucleotide reductase activity is virus-encoded6 and essential for virus replication7. This makes herpesvirus ribonucleotide reductases potential targets for antiviral chemotherapy. The HSV-1-encoded enzyme consists of two summits8,9,18: V136, the large subunit of relative molecular mass (Mr) 136,000 (136K) (RR1), which has been shown to be essential for enzyme activity7, and V38, the small subunit (RR2) which forms a complex with the large subunit and is also likely to be essential for enzyme activity9. Two particular features of the enzyme make it an attractive antiviral target. First, there is evidence for a common, highly conserved herpesvirus ribonucleotide reductase and second, the interaction between the large and small subunits may itself be exploitable. Here we identify a synthetic peptide which specifically inhibits the activity of virus-induced enzyme. We deduce that the mechanism of inhibition involves interference with the normal interaction between the two types of subunit.

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    • Bernadette M. Dutia

    Present address: Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, Edinburgh, EH9 1QH, UK


  1. MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow, G11 5JR, UK

    • Bernadette M. Dutia
    • , Margaret C. Frame
    • , John H. Subak-Sharpe
    • , William N. Clark
    •  & Howard S. Marsden


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