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抗病毒抗生素17997体内外抗病毒作用及抑制机制的研究 被引量:3

THE RESEARCH OF ANTIVIRAL ACTIVITIES IN VITRO AND IN VIVO AND THE INHIBITION MECHANISM OF ANTIVIRAL ANTIBIOTIC 17997
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摘要 17997是由我国云南省思茅地区分离的一株链霉菌所产生的广谱抗病毒抗生素,为非核苷类化合物。在细胞培养内,对单纯疱疹病毒Ⅰ型、Ⅱ型,人免疫缺陷病毒Ⅰ型,水疱性口炎病毒及柯萨奇病毒B_3均有明显抑制作用,IC_(50)在微摩尔或低于微摩尔水平。体内实验对小鼠单纯疱疹病毒Ⅰ型及Ⅱ型脑炎有统计显著性的治疗效果,可降低死亡率,延长小鼠平均生存日;对恒河猴的猴免疫缺陷病毒急性感染,17997预防加治疗给药可降低血浆病毒滴度;对家兔单纯疱疾病毒Ⅰ型角膜炎有统计意义的治疗效果;对豚鼠单纯疱疹病毒Ⅰ型皮肤感染及乳牛乳头纤维瘤均有治疗作用。17997无直接灭活病毒作用,不影响病毒吸附及释放,对病毒核酸聚合酶无抑制活性,可能作用于病毒复制循环的早期阶段。 17997 is a broad spectrum antiviral antibiotic produced by a strain of streptomyces isolated from a soil sample collected in Yunnan Province of China. It is a non-nucleoside compound. 17997 displayed strong inhibitory effects on herpes simplex virus type 1 and type 2, human immunodeficiency virus type 1, vesicular stomatitis vims, coxsackie virus B3 in cell cultures with IC50 values under the lever of μM. In vivo experiments 17997 was effective in treatment of HSV-1 and HSV-2 systematic infections. The mortality of infected mice was reduced and the average survival days of infected mice were extended both with statistical significance. The plasma viral liters of rhesus monkeys infected by simian immunodeficiency virus were reduced by prophylactic and therapeutic treatment of 17997 through ip or sc rout; the treatment efficacy of 17997 against rabbit HSV-1 keratitis was significant, 17997 also displayed therapeutic efficacy against HSV-1 infected guinea pig skin lesions and bovine papilloma virus infected fibropapillomatosis. 17997 did not directly inactivate viral activities and did not affect viral adsorption and release. 17997 did not show any inhibitory effect on viral DNA polymerase and reverse transcriptase. 17997 was still active if the treatment was started within six hours post infection in cell culture. The non-toxic concentration of 17997 could inhibit HSV-1 DNA synthesis significantly without any inhibition on cellular DNA synthesis by isopycnic ultra centrifugation. It seems that 17997 might affect the early stage of virus replication cycle. The great potential of 17997 to develop as an antiviral drug exists.
机构地区 中国医学科学院
出处 《中国科学基金》 CSCD 1999年第1期16-19,共4页 Bulletin of National Natural Science Foundation of China
基金 国家自然科学基金重大项目 批准号39390012
关键词 抗病毒抗生素 单纯疱疹病毒 抗病毒作用 链霉素 antiviral antibiotic 17997, herpes simplex virus, human immunodefficiency virus
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