Document 0090
 DOCN  M9440090
 TI    Inhibition of visna virus replication by 2',3'-dideoxynucleosides and
       acyclic nucleoside phosphonate analogs.
 DT    9404
 AU    Thormar H; Balzarini J; Holy A; Jindrich J; Rosenberg I; Debyser Z;
       Desmyter J; De Clercq E; Institute of Biology, University of Iceland,
       Reykjavik.
 SO    Antimicrob Agents Chemother. 1993 Dec;37(12):2540-4. Unique Identifier :
       AIDSLINE MED/94153023
 AB    A series of acyclic nucleoside phosphonate (ANP) and
       2',3'-dideoxynucleoside (ddN) derivatives were evaluated for their
       inhibitory effects on visna virus replication and maedi/visna
       virus-induced syncytium formation in sheep choroid plexus cells. Most
       ANP derivatives inhibited virus replication and syncytium formation
       within a concentration range of 0.2 to 1.8 microM. Among the most active
       ANP derivatives ranked (R)-9-(2-phosphonomethoxypropyl)adenine,
       (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine, and
       (S)-9-(3-fluoro-2-phosphonomethoxypropyl)adenine. Of the ddN
       derivatives, 2',3'-dideoxycytidine (ddCyd) proved to be the most
       inhibitory to visna virus-induced syncytium formation (50% effective
       concentration, 0.02 microM). The purine ddN analogs (i.e.,
       2',3'-dideoxyinosine, 2',3'-dideoxyadenosine, 2',3'-dideoxyguanosine,
       and 2,6-diaminopurine-2',3'-dideoxyribosine) were 10- to 30-fold less
       effective, and the thymidine derivatives
       2',3'-didehydro-2',3'-dideoxythymidine (D4T) and
       3'-azido-2',3'-dideoxythymidine (AZT) were more than 500-fold less
       inhibitory to visna virus than ddCyd. The 5'-triphosphate forms of AZT
       and D4T were 100- to 600-fold more inhibitory to visna virus
       particle-derived reverse transcriptase than was the 5'-triphosphate of
       ddCyd. The apparent discrepancy between the inhibitory effects of these
       ddN derivatives on virus replication and viral reverse transcriptase
       activity most likely reflects differences in the metabolic conversion of
       ddCyd versus D4T and AZT in sheep choroid plexus cells.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY  Choroid
       Plexus/CYTOLOGY/MICROBIOLOGY  Dideoxynucleosides/*PHARMACOLOGY  HIV/DRUG
       EFFECTS/ENZYMOLOGY  Microbial Sensitivity Tests
       Nucleosides/*PHARMACOLOGY  Phosphonic Acids/*PHARMACOLOGY  Reverse
       Transcriptase/ANTAGONISTS & INHIB  Sheep  Support, Non-U.S. Gov't  Virus
       Replication/*DRUG EFFECTS  Visna-Maedi Virus/*DRUG
       EFFECTS/*PHYSIOLOGY/PATHOGENICITY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).