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1996-03-30
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Document 1046
DOCN M9651046
TI Antiviral activity of a phosphorothioate oligonucleotide complementary
to human cytomegalovirus RNA when used in combination with antiviral
nucleoside analogs.
DT 9505
AU Azad RF; Brown-Driver V; Buckheit RW Jr; Anderson KP; Department of
Infectious Diseases, Isis Pharmaceuticals,; Carlsbad, CA 92008, USA.
SO Antiviral Res. 1995 Oct;28(2):101-11. Unique Identifier : AIDSLINE
MED/96126403
AB ISIS 2922 is a phosphorothioate oligonucleotide with potent antiviral
activity against human cytomegalovirus (HCMV) in cell culture assays.
The ability of ISIS 2922 to inhibit replication of HCMV when used in
combination with other antiviral agents approved for treatment of HCMV
disease was investigated using a 96-well immunoassay. The antiviral
activity of ISIS 2922 against HCMV was additive with that of ganciclovir
(9-(1,3-dihydroxy-2-propoxymethylguanine); DHPG) or foscarnet
(phosphonoformate). Compounds used clinically for the treatment of human
immunodeficiency virus infection and likely to be co-administered with
ISIS 2922 in the clinic were also evaluated for their ability to
modulate the antiviral activity of ISIS 2922. 3'-Azido-3'-deoxythymidine
(AZT) exhibited no antiviral activity against HCMV in the 96-well
immunoassay, and did not significantly alter the antiviral activity of
ISIS 2922. 2'-3'-Dideoxycytidine (ddC) was able to inhibit replication
of HCMV at high doses, and this activity was additive with that of ISIS
2922. ISIS 2922 inhibited HIV replication in acute infection assays at
relatively high concentrations as previously reported for
non-complementary phosphorothioate oligonucleotides. When ISIS 2922 was
used in combination with AZT in this assay, interactions were additive
at most concentrations, although significant and reproducible synergy
was observed at some concentration combinations.
DE Antiviral Agents/*PHARMACOLOGY Cell Line Cytomegalovirus/*DRUG
EFFECTS/GENETICS Drug Interactions DNA Polymerases/ANTAGONISTS & INHIB
Foscarnet/PHARMACOLOGY Ganciclovir/PHARMACOLOGY Human HIV-1/*DRUG
EFFECTS Molecular Sequence Data RNA, Viral Virus Replication/DRUG
EFFECTS Zalcitabine/ANALOGS & DERIVATIVES/PHARMACOLOGY
Zidovudine/PHARMACOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).