Document 0781
 DOCN  M9650781
 TI    Antiviral activity of a phosphorothioate oligonucleotide complementary
       to human cytomegalovirus RNA when used in combination with antiviral
       nucleoside analogs.
 DT    9605
 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).