alpha-Glucosidase inhibitors have a prolonged antiviral effect against hepatitis B virus through the sustained inhibition of the large and middle envelope glycoproteins.
Previous work has shown that the secretion of enveloped hepatitis B virus (HBV) DNA and the HBV middle envelope protein (MHBs) are sensitive to glucosidase inhibition. Here, it is shown that HBV DNA secretion remains depressed after the removal of the glucosidase inhibitor and long after glucosidase function returns to normal. For example, glyco-processing and the secretion of alpha-1 anti-trypsin returned to normal within 3 h of the removal of the glucosidase inhibitor. In contrast, the secretion of HBV did not return to normal for more than 7 days after the removal of the inhibitor. Consistent with the inhibition of HBV virion secretion, the levels of HBV L and HBV M proteins were also reduced by treatment with the glucosidase inhibitor and remained reduced for 7 days after compound withdrawal. The implications of the prolonged antiviral effect against HBV and the use of glucosidase inhibitors as antiviral agents are discussed.
Simsek
Ender
E
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University College of Medicine, Philadelphia, PA, USA.
Lu
Xuanyong
X
Ouzounov
Serguey
S
Block
Timothy M
TM
Mehta
Anand S
AS
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D065089:Glycoside Hydrolase Inhibitors; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors*
D000998:Antiviral Agents; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D065089:Glycoside Hydrolase Inhibitors; C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins; C114312:middle envelope protein, Hepatitis B virus; D017485:1-Deoxynojirimycin; D019259:Lamivudine