Chronic hepatitis B is a viral infection that can currently only be treated with interferon-α and nucleosidic inhibitors of viral polymerase — 3TC and adefovir — but these treatments are limited by serious side effects and a high failure rate. Novel therapeutic regimes are urgently required. In the February 7 Science, Karl Deres and colleagues at the Bayer Research Center, Wuppertal, Germany, describe a substance class for the treatment of HBV infection that displays a highly specific antiviral inhibition of capsid formation, concomitant with a reduced half-life of the core protein (Science 299:893-896, February 7, 2003).

Deres et al. analyzed the in vitro profile and mechanism of action for the heteroaryldihydropyrimidine Bay 41-4109 and the congeners Bay 38-7690 and Bay 39-5493.They observed that Bay 41-4109 blocked by 50% the HBV replication when incubated with HBV-producing HepG2.2.15 cells. In addition, they showed that Bay 41-4109 and Bay 38-7690 reduced HBV core protein levels in cell culture and induced depletion of newly synthesized core proteins.

"The candidate, Bay 41-4109, may become a valuable addition to future [anti-HBV] therapy (mono- or combination-therapy regimens) in light of its specific mechanism of action," conclude the authors.