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.