| Literature DB >> 11120971 |
M L Bryant1, E G Bridges, L Placidi, A Faraj, A G Loi, C Pierra, D Dukhan, G Gosselin, J L Imbach, B Hernandez, A Juodawlkis, B Tennant, B Korba, P Cote, P Marion, E Cretton-Scott, R F Schinazi, J P Sommadossi.
Abstract
A unique series of simple "unnatural" nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3'-OH group of the beta-L-2'-deoxyribose of the beta-L-2'-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides beta-L-2'-deoxycytidine, beta-L-thymidine, and beta-L-2'-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (alpha, beta, and gamma) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 10(8) genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.Entities:
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Year: 2001 PMID： 11120971 PMCID： PMC90266 DOI： 10.1128/AAC.45.1.229-235.2001
Source DB: PubMed Journal: Antimicrob Agents Chemother ISSN： 0066-4804 Impact factor: 5.191