Anti-HBV specific beta-L-2'-deoxynucleosides |
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Authors: | Bryant M L Bridges E G Placidi L Faraj A Loi A G Pierra C Dukhan D Gosselin G Imbach J L Hernandez B Juodawlkis A Tennant B Korba B Cote P Cretton-Scott E Schinazi R F Sommadossi J P |
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Affiliation: | Novirio Pharmaceuticals, Inc., 125 Cambridge Park Dr., Cambridge, Massachussetts 02476, USA. bryant.martin@novirio.com |
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Abstract: | A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules have in common a hydroxyl group in the 3'-position (3'-OH) of the beta-L-2'-deoxyribose sugar that confers antiviral activity specifically against hepadnaviruses. Replacement of the 3'-OH broadens activity to other viruses. Substitution 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. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection. |
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