Inhibitory effects of 2'-fluorinated arabinosyl-pyrimidine nucleosides on woodchuck hepatitis virus replication in chronically infected woodchucks.
The treatment of woodchuck hepatitis virus infections with 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU), given intraperitoneally, caused complete and permanent decrease of serum virus endogenous DNA polymerase and viral DNA in all treated woodchucks but was associated with severe toxicity. By contrast 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil (FEAU) induced a sustained, although less dramatic, decrease of viral replication without apparent toxic effect. FEAU was also effective when given orally. However, in both cases this inhibitory effect was transient.
Fourel
I
I
Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus Humains, Institut National de la Santé et de la Recherche Médicale U 271, Lyon, France.
Hantz
O
O
Watanabe
K A
KA
Jacquet
C
C
Chomel
B
B
Fox
J J
JJ
Trepo
C
C
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002908:Chronic Disease; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015613:Hepadnaviridae / Q000187:drug effects* / Q000502:physiology; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy* / Q000382:microbiology; D014529:Uridine / Q000031:analogs & derivatives*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D003561:Cytarabine; D001086:Arabinofuranosyluracil; C026023:fiacitabine; C054103:2'-fluoro-5-ethylarabinosyluracil; C034935:clevudine; D014529:Uridine