title: Anti-HBV specific beta-L-2'-deoxynucleosides.
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.
authors.affiliation: Novirio Pharmaceuticals, Inc., 125 Cambridge Park Dr., Cambridge, Massachussetts 02476, USA. bryant.martin@novirio.com
authors.forename: M L
authors.initials: ML
authors.lastname: Bryant
authors.forename: E G
authors.initials: EG
authors.lastname: Bridges
authors.forename: L
authors.initials: L
authors.lastname: Placidi
authors.forename: A
authors.initials: A
authors.lastname: Faraj
authors.forename: A G
authors.initials: AG
authors.lastname: Loi
authors.forename: C
authors.initials: C
authors.lastname: Pierra
authors.forename: D
authors.initials: D
authors.lastname: Dukhan
authors.forename: G
authors.initials: G
authors.lastname: Gosselin
authors.forename: J L
authors.initials: JL
authors.lastname: Imbach
authors.forename: B
authors.initials: B
authors.lastname: Hernandez
authors.forename: A
authors.initials: A
authors.lastname: Juodawlkis
authors.forename: B
authors.initials: B
authors.lastname: Tennant
authors.forename: B
authors.initials: B
authors.lastname: Korba
authors.forename: P
authors.initials: P
authors.lastname: Cote
authors.forename: E
authors.initials: E
authors.lastname: Cretton-Scott
authors.forename: R F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: J P
authors.initials: JP
authors.lastname: Sommadossi
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000737:chemistry / Q000494:pharmacology; D003841:Deoxycytidine / Q000737:chemistry / Q000494:pharmacology; D003853:Deoxyribonucleosides / Q000737:chemistry / Q000494:pharmacology*; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy; D006801:Humans; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013936:Thymidine / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D003839:Deoxyadenosines; D003853:Deoxyribonucleosides; D003841:Deoxycytidine; D013936:Thymidine