Antiviral activity of a phosphorothioate oligonucleotide complementary to human cytomegalovirus RNA when used in combination with antiviral nucleoside analogs
- PMID: 8585764
- DOI: 10.1016/0166-3542(95)00035-k
Antiviral activity of a phosphorothioate oligonucleotide complementary to human cytomegalovirus RNA when used in combination with antiviral nucleoside analogs
Abstract
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.
Similar articles
-
Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early region.Antimicrob Agents Chemother. 1993 Sep;37(9):1945-54. doi: 10.1128/AAC.37.9.1945. Antimicrob Agents Chemother. 1993. PMID: 8239610 Free PMC article.
-
Combinations of 3'-azido-3'-deoxythymidine (zidovudine) and phosphonoformate (foscarnet) against human immunodeficiency virus type 1 and cytomegalovirus replication in vitro.Antimicrob Agents Chemother. 1989 May;33(5):663-9. doi: 10.1128/AAC.33.5.663. Antimicrob Agents Chemother. 1989. PMID: 2546487 Free PMC article.
-
The antisense oligonucleotide ISIS 2922 prevents cytomegalovirus-induced upregulation of IL-8 and ICAM-1 in cultured human fibroblasts.J Med Virol. 2000 Mar;60(3):313-23. doi: 10.1002/(sici)1096-9071(200003)60:3<313::aid-jmv10>3.0.co;2-k. J Med Virol. 2000. PMID: 10630964
-
[Recent advances in antiviral drugs--antiviral agents to HCMV, HHV-6, and HHV-7].Nihon Rinsho. 1998 Jan;56(1):140-4. Nihon Rinsho. 1998. PMID: 9465679 Review. Japanese.
-
Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections.Drugs. 1994 Aug;48(2):199-226. doi: 10.2165/00003495-199448020-00007. Drugs. 1994. PMID: 7527325 Review.
Cited by
-
Inhibition of human cytomegalovirus immediate-early gene expression by an antisense oligonucleotide complementary to immediate-early RNA.Antimicrob Agents Chemother. 1996 Sep;40(9):2004-11. doi: 10.1128/AAC.40.9.2004. Antimicrob Agents Chemother. 1996. PMID: 8878571 Free PMC article.
-
Phosphorothioate oligonucleotides derived from human immunodeficiency virus type 1 (HIV-1) primer tRNALys3 are strong inhibitors of HIV-1 reverse transcriptase and arrest viral replication in infected cells.Antimicrob Agents Chemother. 1997 Oct;41(10):2141-8. doi: 10.1128/AAC.41.10.2141. Antimicrob Agents Chemother. 1997. PMID: 9333039 Free PMC article.
-
miRCOVID-19: Potential Targets of Human miRNAs in SARS-CoV-2 for RNA-Based Drug Discovery.Noncoding RNA. 2021 Mar 2;7(1):18. doi: 10.3390/ncrna7010018. Noncoding RNA. 2021. PMID: 33801496 Free PMC article.
-
Fomivirsen.Drugs. 1999 Mar;57(3):375-80; discussion 381. doi: 10.2165/00003495-199957030-00010. Drugs. 1999. PMID: 10193689 Review.
-
Combined Treatment with Host-Directed and Anticytomegaloviral Kinase Inhibitors: Mechanisms, Synergisms and Drug Resistance Barriers.Pharmaceutics. 2023 Nov 27;15(12):2680. doi: 10.3390/pharmaceutics15122680. Pharmaceutics. 2023. PMID: 38140021 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources