Abstract
Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-alpha and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and the substantial resistance of the virus to nucleosidic inhibitors. Potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired. We describe non-nucleosidic inhibitors of HBV nucleocapsid maturation that possess in vitro and in vivo antiviral activity. These inhibitors have potential for future therapeutic regimens to combat chronic HBV infection.
MeSH terms
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Acetylcysteine / analogs & derivatives*
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Acetylcysteine / pharmacology
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Amino Acid Substitution
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Antiviral Agents / chemistry
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Antiviral Agents / metabolism
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Antiviral Agents / pharmacology*
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Binding Sites
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Capsid / metabolism
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DNA Replication / drug effects
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DNA, Viral / biosynthesis
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Half-Life
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Hepatitis B Virus, Duck / drug effects
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Hepatitis B Virus, Duck / metabolism
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Hepatitis B virus / drug effects*
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Hepatitis B virus / physiology
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Humans
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Mutation
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Nucleocapsid / metabolism*
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Pyridines / chemistry
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Pyridines / metabolism
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Pyridines / pharmacology*
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Pyrimidines / chemistry
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Pyrimidines / metabolism
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Pyrimidines / pharmacology*
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Recombinant Proteins / metabolism
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Stereoisomerism
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Triazoles / chemistry
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Triazoles / metabolism
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Triazoles / pharmacology*
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Tumor Cells, Cultured
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Viral Core Proteins / chemistry
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Viral Core Proteins / genetics
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Viral Core Proteins / metabolism
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Virus Assembly / drug effects
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Virus Replication / drug effects
Substances
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Antiviral Agents
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BAY 38-7690
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BAY 39-5493
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BAY 41-4109
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DNA, Viral
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Pyridines
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Pyrimidines
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Recombinant Proteins
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Triazoles
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Viral Core Proteins
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lactacystin
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Acetylcysteine