Inhibition of episomal hepatitis B virus DNA in vitro by 2,4-diamino-7- (2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine.

Abstract

The nucleoside analog 2,4-diamino-7-(2-deoxy-2-fluoro-beta-D- arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (T70080) and several related compounds were evaluated for anti-hepatitis B virus (HBV) activity by using cultured 2.2.15 cells. T70080 reduced episomal viral replication in these cells by 50% at a concentration of 0.7 microgram/ml. At the same time, T70080 reduced cellular proliferation by 50% at a concentration in excess of 100 micrograms/ml, yielding a therapeutic index of > 143. In cells cultured for 12 days in the presence of 10 or 50 micrograms of T70080 per ml and then with drug-free medium, for an additional 12 days, viral DNA replication was completely inhibited initially but resumed between 6 and 12 days post-drug removal. In view of the potent anti-HBV activity shown, T70080 is a good candidate for further evaluation as a treatment of human HBV infection.

• Authors: J O Ojwang, B K Bhattacharya, H B Marshall, B E Korba, G R Revankar, R F Rando
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 39 Issue 11 Pg. 2570-3 (Nov 1995) ISSN: 0066-4804 [Print] United States
• PMID: 8585748 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Arabinonucleosides
• DNA, Viral
• T 70080

Topics

• Antiviral Agents (pharmacology)
• Arabinonucleosides (pharmacology)
• Cell Line
• DNA Replication (drug effects)
• DNA, Viral (biosynthesis, isolation & purification)
• Hepatitis B virus (drug effects, genetics, physiology)
• Humans
• Immunoblotting
• Plasmids (drug effects)
• Tumor Cells, Cultured
• Virus Replication (drug effects)