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M9651051.TXT
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1996-03-30
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Document 1051
DOCN M9651051
TI Some nucleoside analogs with anti-human immunodeficiency virus activity
inhibit replication of Epstein-Barr virus.
DT 9505
AU Mar EC; Chu CK; Lin JC; Tumor Virology Laboratory, Centers for Disease
Control and; Prevention, Atlanta, GA 30333, USA.
SO Antiviral Res. 1995 Sep;28(1):1-11. Unique Identifier : AIDSLINE
MED/96105493
AB The effects of (+)-beta-D-dioxolane-cytosine ((+)-D-beta-DOC),
(-)-beta-L-dioxolane-cytosine ((-)-L-beta-DOC),
(+)-beta-D-oxathiolane-cytosine ((+)-D-beta-OTC),
(-)-beta-L-oxathiolane-cytosine ((-)-L-beta-OTC, or 3TC),
3'-azido-2',3'-dideoxy-5-methyl-cytidine (5-Me-AZDC), and
3'-azido-2',3'-dideoxyuridine (AZDU) on Epstein-Barr virus (EBV) DNA
replication in vitro were tested in P3HR-1 cells. Two anti-EBV drugs,
3'-azido-3'-deoxythymidine (AZT) and
9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, or ganciclovir), were
used as positive controls. The inhibitory effects on EBV DNA synthesis
were quantified by membrane filter and Southern blot hybridizations with
an EBV-specific probe BamHI-W fragment. The 50% effective doses (ED50)
for EBV DNA replication were 0.15, 0.83, 1.5, 8.3, 14, and 7.7 microM
for DHPG, (-)-L-beta-DOC, (+)-D-beta-DOC, (+)-D-beta-OTC,
(-)-L-beta-OTC, and AZT, respectively. In contrast, 5-Me-AZDC and AZDU
were not effective at concentrations as high as 30 microM. These results
indicated that both (-)-L-beta-DOC and (+)-D-beta-DOC were more potent
than AZT, which has previously been shown to have anti-EBV activity.
(-)-L-beta-DOC and (+)-D-beta-DOC have also been previously demonstrated
to suppress the infectivity of human immunodeficiency virus type 1
(HIV-1). Thus, (-)-L-beta-DOC represents the first nucleoside analog
with L-configuration exhibiting significant antiviral activities against
both EBV and HIV.
DE Antiviral Agents/*PHARMACOLOGY Cell Line DNA, Viral/ANALYSIS
Herpesvirus 4, Human/*DRUG EFFECTS/GENETICS Human HIV-1/DRUG EFFECTS
Nucleosides/*PHARMACOLOGY Structure-Activity Relationship Support,
U.S. Gov't, P.H.S. JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).