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JAC Advance Access published online on November 12, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg490
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Leading article

Prenylation inhibitors: a novel class of antiviral agents

Shirit Einav 1 and Jeffrey S. Glenn 1 *

1 Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94305-5187, USA

* Corresponding author. E-mail: jeffrey.glenn{at}stanford.edu.

Abstract

Prenylation is a site-specific lipid modification of proteins. Although first described for a variety of cellular proteins, it has become apparent that viruses can also make use of this post-translational modification provided by their host cells. Depriving a virus access to prenylation can have dramatic effects on the targeted virus’s life cycle. Selective pharmacological inhibitors of prenylating enzymes have been developed and shown to have potent antiviral effects in both in vitro and in vivo systems. Because prenylation inhibitors target a host cell function, are available in oral form and are surprisingly well tolerated in human trials, these compounds represent an attractive new class of antiviral agents with potential for broad-spectrum activity. After a brief outline of host cell prenylation pathways, we review below the development of prenylation inhibition as an antiviral strategy applied to a prototype target, hepatitis delta virus (HDV), and discuss the potential application of prenylation inhibitors to a broad range of other viruses.

Keywords: farnesyltransferase inhibitors, hepatitis delta virus, antiviral therapy
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