Anti-HBV specific beta-L-2 '-deoxynucleosides

A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules h ave in common a hydroxyl group in the 3'-position (3'-OH) of the beta -L-2' -deoxyribose sugar that confers antiviral activity specifically against hep adnaviruses. Replacement of the 3'-OH broadens activity to other viruses, S ubstitution in the base decreases antiviral potency and selectivity. Human DNA polymerases and mitochondrial function are not effected. Plasma viremia is reduced up to 8 logs in a woodchuck model of chronic HBV infection. The se investigational drugs, used alone or in combination, are expected to off er new therapeutic options for patients with chronic HBV infection.