Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: therapeutic implications.

Journal article

Previously we have shown that the imino sugar inhibitor of N-linked glycan processing, N-nonyl-deoxynojirimycin (N-nonyl-DNJ), had antiviral activity in the woodchuck model of chronic hepatitis B virus (HBV) infection. In studying the mechanism of action of this compound, it was discovered that imino sugars could inhibit HBV secretion without inhibiting N-linked glycoprocessing. Although N-nonyl-DNJ is an inhibitor of the endoplasmic reticulum (ER) glucosidase, here it is shown that N-nonyl-DNJ retained antiviral activity at concentrations that had no significant impact on ER glucosidase function. Taken together, these results suggested that N-nonyl-DNJ possessed an antiviral activity attributable to a function other than an impact on glycoprocessing. This hypothesis was confirmed by experiments showing that N-nonyl-deoxygalactojirimycin (N-nonyl-DGJ), an alkyl derivative of galactose with no impact on glycoprocessing, retains anti-HBV activity. The data suggest that N-nonyl-DGJ exerts its antiviral action at a point before viral envelopment and may prevent the proper encapsidation of the HBV pregenomic RNA.

Authors: Mehta, A; Carrouée, S; Conyers, B; Jordan, R; Butters, T

• Publication status: Published
• Journal: Hepatology (Baltimore, Md.)
• Volume: 33
• Issue: 6
• Pages: 1488-1495
• Publication date: 2001-06-01
• DOI: 10.1053/jhep.2001.25103
• EISSN: 1527-3350
• ISSN: 0270-9139
• Language: English
• Keywords: 1-Deoxynojirimycin; Hepatitis B virus; Polysaccharides; Cattle; alpha-Glucosidases; Animals; Gene Products, pol; Cell Line; DNA, Viral; Antiviral Agents; DNA Replication; Intracellular Membranes; DNA-Directed DNA Polymerase