Glucosidase inhibitors may have a future as broad-based hepatitis drugs Researchers at Jefferson Medical College may have found a promising drug against the hepatitis C virus (HCV). While they are quick to point out that the drug, N-nonyl-DNJ, stopped only a surrogate virus - and not the actual HCV - from reproducing in the laboratory, they believe the findings, which build on their earlier success against hepatitis B virus (HBV), may someday lead to a single drug against both viruses.
Timothy Block, Ph.D., professor of biochemistry and molecular pharmacology and medicine at Thomas Jefferson University in Philadelphia, and colleagues at Oxford University in Oxford, UK, used the drug to inhibit the activity of an important cellular enzyme, glucosidase. This in turn prevented the bovine diarrhea virus, BVDV, which is a tissue culture model of HCV, from making more virus. Dr. Block believes this class of drugs, called glucosidase inhibitors, "have a reasonable likelihood of working against HCV therapeutically." Because HCV cannot be grown in the lab, researchers use BVDV as a testing model.
"This is the first drug since alpha-interferon to my knowledge for which there is published experimental evidence against HCV - in the form of BVDV susceptibility," says Dr. Block, who is a member of Jefferson's Kimmel Cancer Center and director of the Jefferson Center for Biomedical Research and Agricultural Medicine.
The drug may sidestep resistant viruses, the bane of current anti-hepatitis treatments. "Since the drugs target a host cellular enzyme at very non-toxic doses, rather than the virus, we think that resistance to the drugs will not be a problem,"he says.
The findings appear Oct. 12 in the Proceedings of the National Academy
of Sciences.
Viruses such as HCV, HBV and BVDV reproduce by actually "budding out
from intracellular membranes." The viruses
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
215-955-5291
Thomas Jefferson University
11-Oct-1999