Activity of New Anti-HBV Agents Elucidated

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Activity of New Anti-HBV Agents Elucidated

NEW YORK (Reuters Health) Feb 06 - A new class of compounds, known as

heteroaryldihydropyrimidines (HAPs), has been shown to inhibit hepatitis B

virus (HBV) replication in the laboratory and in vivo. Now, new study

findings suggest that this anti-HBV activity is due to inhibition of

nucleocapsid formation.

Currently, interferon-alpha and nucleosidic inhibitors of HBV polymerase are

the only drugs approved for the treatment of chronic HBV infection, lead

author Dr. Karl Deres, from Bayer Research Center in Wupertal, Germany, and

colleagues note.

However, interferon-alpha is associated with dose-limiting side effects and

HBV strains often develop resistance to the polymerase inhibitors.

Therefore, new anti-HBV agents with different mechanisms of action are

needed, the researchers note.

Unlike other agents, HAPs are non-nucleosidic and do not inhibit the HBV

polymerase, the investigators note. Although they have been shown to be

highly potent inhibitors of HBV replication, their exact mechanism of action

has been unclear.

In a study reported in the February 7th issue of Science, Dr. Deres' team

analyzed the activity of these drugs in cell culture. The researchers found

that the HAPs work by inhibiting formation of the nucleocapsids needed for

viral replication. This was associated with a reduction in core protein

levels.

Of the various HAPs tested, one (Bay 41-4109) has shown particular promise

as a potential therapeutic agent. " It has a demonstrated efficacy in HBV

transgenic mice and a suitable preclinical pharmacokinetic and toxicology

profile, " the authors note. " The clinical efficacy of this treatment...will

now need to be demonstrated. "

Science 2003;299:893-896.