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新型免疫增强剂7-硫杂-8-氧代鸟苷的广谱体内抗病毒活性

Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine, a novel immunopotentiating agent.

作者信息

Smee D F, Alaghamandan H A, Cottam H B, Sharma B S, Jolley W B, Robins R K

机构信息

Nucleic Acid Research Institute, Costa Mesa, California 92626.

出版信息

Antimicrob Agents Chemother. 1989 Sep;33(9):1487-92. doi: 10.1128/AAC.33.9.1487.

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.

摘要

一种新型免疫增强剂,5-氨基-3-β-D-呋喃核糖基噻唑并[4,5-d]嘧啶-2,7(3H,6H)-二酮(7-硫杂-8-氧代鸟苷),在体外缺乏病毒抑制特性,但可诱导干扰素并增强免疫功能,如自然杀伤细胞活性。在啮齿动物模型中对其进行评估,以确定抗病毒活性谱和有效治疗方案。在病毒接种前1天以50至200mg/kg的剂量单次或分次腹腔内注射,可显著保护经腹腔感染Semliki森林病毒、圣安杰洛病毒、班齐病毒和脑心肌炎病毒的小鼠。同样,乳鼠可免受大鼠冠状病毒的鼻内攻击。对于圣安杰洛病毒,治疗可延迟至病毒接种后1天,仍显示出有益效果。该化合物对经腹腔感染2型单纯疱疹病毒或经鼻感染水疱性口炎病毒的小鼠有中等疗效。当该类似物在病毒接种前单次给药或在病毒接种前后多次给药时,对小鼠的乙型流感病毒无活性。对小鼠的疱疹性皮肤损伤也没有预防作用。这种免疫调节剂可能有望用于治疗多种病毒感染。

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