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Nucleosides, Nucleotides & Nucleic Acids Volume 20, 2001 - Issue 4-7
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Original Articles

ANTI-HBV SPECIFIC β-L-2′-DEOXYNUCLEOSIDES

Martin L. Bryant Novirio Pharmaceuticals, Inc., 125 CambridgePark Dr., Cambridge, Massachussetts, 02476; Novirio Pharmaceuticals, Inc., 125 CambridgePark Drive, Cambridge, MA, 02476, U.S.A.Correspondence[email protected]
,
Edward G. Bridges Novirio Pharmaceuticals, Inc., 125 CambridgePark Dr., Cambridge, Massachussetts, 02476
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Laurent Placidi Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, The Liver Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, U.S.A.
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Abdesslem Faraj Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, The Liver Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, U.S.A.
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Anna-Giulia Loi Novirio Pharmaceuticals, SARL, 23-25 rue de Berri, Paris, 75008, France
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Claire Pierra Novirio Pharmaceuticals, SARL, 23-25 rue de Berri, Paris, 75008, France
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David Dukhan Novirio Pharmaceuticals, SARL, 23-25 rue de Berri, Paris, 75008, France
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Gilles Gosselin Universite de Montpellier II, Laboratoire de Chimie Bioorganique, CNRS UMR 5625, Place Eugene Bataillon, 34095, Cedex 5, Montpellier, France
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Jean-Louis Imbach Universite de Montpellier II, Laboratoire de Chimie Bioorganique, CNRS UMR 5625, Place Eugene Bataillon, 34095, Cedex 5, Montpellier, France
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Brenda Hernandez Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, The Liver Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, U.S.A.
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Amy Juodawlkis Novirio Pharmaceuticals, Inc., 125 CambridgePark Dr., Cambridge, Massachussetts, 02476
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Bud Tennant Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, 14853, U.S.A.
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Brent Korba Division of Molecular Virology and Immunology, Georgetown University College of Medicine, Rockville, Maryland, 20852, U.S.A.
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Paul Cote Division of Molecular Virology and Immunology, Georgetown University College of Medicine, Rockville, Maryland, 20852, U.S.A.
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Erika Cretton-Scott Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, The Liver Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, U.S.A.
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Raymond F. Schinazi Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, California, 30033, U.S.A.
&
Jean-Pierre Sommadossi Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, The Liver Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, U.S.A.
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Pages 597-607 | Published online: 07 Feb 2007
 
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Abstract

A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules have in common a hydroxyl group in the 3′-position (3′-OH) of the β-L-2′-deoxyribose sugar that confers antiviral activity specifically against hepadnaviruses. Replacement of the 3′-OH broadens activity to other viruses. Substitution in the base decreases antiviral potency and selectivity. Human DNA polymerases and mitochondrial function are not effected. Plasma viremia is reduced up to 8 logs in a woodchuck model of chronic HBV infection. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

Acknowledgments

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