Use of a prenylation inhibitor as a novel antiviral agent.
No specific therapy exists for hepatitis delta virus (HDV), which can cause severe liver disease. Molecular genetic studies have implicated the prenylation site of large delta antigen as a critical determinant of HDV particle assembly. We have established a cell culture model which produces HDV-like particles, and we show that delta antigen prenylation can be pharmacologically inhibited by the prenylation inhibitor BZA-5B. Furthermore, BZA-5B specifically abolishes particle production in a dose-dependent manner. These results demonstrate that the use of such a prenylation inhibitor-based antiviral therapy may be feasible and identify a novel class of potential antiviral agents.
Division of Gastroenterology, Stanford University School of Medicine and Veterans Administration Medical Center, Palo Alto, California 94305-5487, USA. Jeffrey.glen@stanford.edu
J S
JS
Glenn
J C
JC
Marsters
H B
HB
Greenberg
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D003699:Hepatitis D / Q000188:drug therapy; D003698:Hepatitis Delta Virus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D017368:Protein Prenylation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; C090156:BZA 5B; D009842:Oligopeptides; D001569:Benzodiazepines