Antiviral L-nucleosides specific for hepatitis B virus infection.

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.

• Authors: M L Bryant, 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
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 45 Issue 1 Pg. 229-35 (Jan 2001) ISSN: 0066-4804 [Print] United States
• PMID: 11120971 (Publication Type: Journal Article)

Chemical References

• Anti-HIV Agents
• Antiviral Agents
• DNA, Viral
• Deoxyadenosines
• Nucleosides
• Deoxycytidine
• DNA-Directed DNA Polymerase
• Thymidine

Topics

• Animals
• Anti-HIV Agents (pharmacology)
• Antiviral Agents (pharmacology, therapeutic use)
• Bone Marrow Cells (drug effects)
• Cell Line
• DNA, Viral (biosynthesis)
• DNA-Directed DNA Polymerase (metabolism)
• Deoxyadenosines (pharmacology, therapeutic use)
• Deoxycytidine (pharmacology, therapeutic use)
• Female
• HIV-1 (drug effects)
• Hepatitis B (drug therapy, virology)
• Hepatitis B virus (drug effects)
• Humans
• Male
• Marmota
• Nucleosides (pharmacology, therapeutic use)
• Stem Cells (drug effects)
• Thymidine (pharmacology, therapeutic use)
• Virus Replication (drug effects)