Chronic hepatitis B virus (HBV) infection is a major cause of liver disease.
However, at this stage only interferon-alpha and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy.
These therapies are limited by the side effects of interferon, and by the substantial resistance of the virus to nucleosidic inhibitors.
|Heteroaryldihydropyrimidines prevent the proper formation of viral core particles.|
Therefore, potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired.
In this study, researchers from Germany explored the drug profile and mechanisms of 2 compounds (Bay 38-7690 and Bay 39-5493), known as heteroaryldihydropyrimidines (HAP).
HAP prevents the proper formation of viral core particles (nucleocapsids), which are the site of viral DNA replication.
The team determined that Bay 38-7690 treatment interfered with the formation of core particles, without affecting core protein levels.
In addition, the team investigated binding between tritium-labeled Bay 39-5493 and HBV core particles. Binding was found to be specific for the human virus, enantio-selective and reversible.
Dr Karl Deres's team concluded, “We present a substance class for the treatment of HBV infection that displays a highly specific antiviral principle, namely, inhibition of capsid formation, concomitant with a reduced half-life of the core protein.”
“The clinical efficacy of this treatment modality of HBV infection will now need to be demonstrated”.