Document Detail

Amantadine inhibits the function of an ion channel encoded by GB virus B, but fails to inhibit virus replication.
MedLine Citation:
PMID:  16759044     Owner:  NLM     Status:  MEDLINE    
A chemically synthesized peptide representing the C-terminal subunit (p13-C) of the p13 protein of GB virus B (GBV-B), the most closely related virus to hepatitis C virus (HCV) showed ion channel activity in artificial lipid bilayers. The channels had a variable conductance and were more permeable to potassium ions than to chloride ions. Amantadine but not hexamethylene amiloride (HMA) inhibited the ion channel function of p13-C in the lipid membranes. However, neither agent was able to inhibit the replication and secretion of GBV-B from virus-infected cultured marmoset hepatocytes, which were harvested from a marmoset that was infected in vivo or inhibit replication after in vitro infection of naive hepatocytes. These data suggest that the GBV-B ion channel, contrary to the data derived from the lipid membranes, is either resistant to amantadine or that virus replication and secretion are independent of ion channel function. As the p7 protein of HCV also has ion channel activity that is apparently resistant to amantadine in vivo, the former possibility is most likely. Ion channels are likely to have an important role in the life cycle of many viruses and compounds that block these channels may prove to be useful antiviral agents.
Anita Premkumar; Xuebin Dong; Gholamreza Haqshenas; Peter W Gage; Eric J Gowans
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antiviral therapy     Volume:  11     ISSN:  1359-6535     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2006  
Date Detail:
Created Date:  2006-06-08     Completed Date:  2006-07-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  289-95     Citation Subset:  IM    
John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia.
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MeSH Terms
Amantadine / pharmacology*
Amino Acid Sequence
Antiviral Agents / pharmacology*
Cells, Cultured
Flaviviridae Infections / virology
GB virus B / drug effects*,  genetics,  metabolism,  physiology
Hepatitis, Viral, Animal / virology
Hepatocytes / virology
Ion Channels / chemistry,  drug effects*,  genetics,  metabolism
Lipid Bilayers
Molecular Sequence Data
Viral Proteins / chemistry,  genetics*,  metabolism
Virus Replication / drug effects*
Reg. No./Substance:
0/Antiviral Agents; 0/Ion Channels; 0/Lipid Bilayers; 0/Viral Proteins; 768-94-5/Amantadine

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