title: Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine, a novel immunopotentiating agent.
abstract: A novel immunopotentiating agent, 5-amino-3-beta-D-ribofuranosylthiazolo [4,5-d]pyrimidine-2,7(3H,6H)-dione (7-thia-8-oxoguanosine), lacks virus-inhibitory properties in vitro but induces interferon and potentiates immune functions, such as natural killer cell activity. It was evaluated in rodent models to determine the spectrum of antiviral activity and effective treatment regimens. At 50 to 200 mg/kg given as single or divided intraperitoneal (i.p.) doses 1 day before virus inoculation, significant protection was afforded to mice infected i.p. with Semliki Forest, San Angelo, banzi, and encephalomyocarditis viruses. Similarly, suckling rats were protected from an intranasal challenge with rat coronavirus. Against San Angelo virus, treatments could be delayed to 1 day post-virus inoculation and still show a beneficial effect. The compound was moderately effective in mice infected i.p. with herpes simplex virus type 2 or intranasally with vesicular stomatitis virus. No activity was seen against influenza B virus in mice when the analog was administered one time pre-virus inoculation or in multiple doses given before and after the virus inoculation. Nor was there a prophylactic effect against herpetic skin lesions on mice. This immune modulator may have promise for the treatment of a variety of virus infections.
authors.affiliation: Nucleic Acid Research Institute, Costa Mesa, California 92626.
authors.forename: D F
authors.initials: DF
authors.lastname: Smee
authors.forename: H A
authors.initials: HA
authors.lastname: Alaghamandan
authors.forename: H B
authors.initials: HB
authors.lastname: Cottam
authors.forename: B S
authors.initials: BS
authors.lastname: Sharma
authors.forename: W B
authors.initials: WB
authors.lastname: Jolley
authors.forename: R K
authors.initials: RK
authors.lastname: Robins
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000833:Animals, Suckling; D000998:Antiviral Agents; D005260:Female; D006151:Guanosine / Q000494:pharmacology / Q000031:analogs & derivatives; D007369:Interferon Inducers; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D011247:Pregnancy; D051381:Rats; D014777:Virus Diseases / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D007369:Interferon Inducers; D006151:Guanosine; C061136:isatoribine