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.
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.
Ojwang
J O
JO
Triplex Pharmaceutical Corporation, The Woodlands, Texas 77380, USA.
Bhattacharya
B K
BK
Marshall
H B
HB
Korba
B E
BE
Revankar
G R
GR
Rando
R F
RF
D000998:Antiviral Agents / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000494:pharmacology*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis* / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D010957:Plasmids / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001087:Arabinonucleosides; D004279:DNA, Viral; C098175:T 70080