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多种1-β-D-阿拉伯呋喃糖基-E-5-卤代乙烯基尿嘧啶和E-5-溴乙烯基-2'-脱氧尿苷对鲑疱疹病毒、马苏大麻哈鱼病毒(OMV)的抗病毒活性。

Antiviral activity of various 1-beta-D-arabinofuranosyl-E-5-halogenovinyluracils and E-5-bromovinyl-2'-deoxyuridine against salmon herpes virus, Oncorhynchus masou virus (OMV).

作者信息

Suzuki S, Machida H, Saneyoshi M

出版信息

Antiviral Res. 1987 Feb;7(2):79-86. doi: 10.1016/0166-3542(87)90023-4.

DOI:10.1016/0166-3542(87)90023-4
PMID:3034148
Abstract

1-beta-D-Arabinofuranosyl-E-5-bromovinyluracil (BVaraU), 1-beta-D-arabinofuranosyl-E-5-iodovinyluracil (IVaraU), 1-beta-D-arabinofuranosyl-E-5-chlorovinyluracil (CVaraU) and 1-beta-D-arabinofuranosyl-5-vinyluracil (VaraU) were examined for antiviral activity against salmon herpesvirus, Oncorhynchus masou virus (OMV) in vitro using Yamame (Oncorhynchus masou) kidney cells (YNK). BVaraU, IVaraU, CVaraU and VaraU were highly active against OMV; 50% inhibitory concentration (IC50): 0.01, 0.003, 0.003, 0.003 microgram/ml, respectively. The IC50 of 5-bromovinyl-2'-deoxyuridine (BVDU) was 0.3 microgram/ml. The lower activity may be due to cleavage of it N-glycosyl linkage by pyrimidine nucleoside phosphorylases (i.e. thymidine phosphorylase) during the incubation period. The arabinofuranosyl counterparts are resistant to this (these) enzyme(s). Both OMV-induced DNA polymerase and cellular DNA polymerase alpha were strongly inhibited by BVaraU 5'-triphosphate (BVaraUTP). In an in vivo study, daily immersion of OMV-infected chum salmon (Oncorhynchus keta) fry into aqueous solution of BVaraU (5 micrograms/ml, 30 min/day, 30 times) did not increase the life span of infected fish.

摘要

对1-β-D-阿拉伯呋喃糖基-E-5-溴乙烯基尿嘧啶(BVaraU)、1-β-D-阿拉伯呋喃糖基-E-5-碘乙烯基尿嘧啶(IVaraU)、1-β-D-阿拉伯呋喃糖基-E-5-氯乙烯基尿嘧啶(CVaraU)和1-β-D-阿拉伯呋喃糖基-5-乙烯基尿嘧啶(VaraU)进行了研究,以考察它们在体外对鲑疱疹病毒、马苏大麻哈鱼病毒(OMV)的抗病毒活性,使用山女鳟(马苏大麻哈鱼)肾细胞(YNK)进行实验。BVaraU、IVaraU、CVaraU和VaraU对OMV具有高活性;50%抑制浓度(IC50)分别为:0.01、0.003、0.003、0.003微克/毫升。5-溴乙烯基-2'-脱氧尿苷(BVDU)的IC50为0.3微克/毫升。其活性较低可能是由于在孵育期间它的N-糖苷键被嘧啶核苷磷酸化酶(即胸苷磷酸化酶)裂解。阿拉伯呋喃糖基类似物对这种(这些)酶具有抗性。OMV诱导的DNA聚合酶和细胞DNA聚合酶α均被BVaraU 5'-三磷酸(BVaraUTP)强烈抑制。在一项体内研究中,将感染OMV的大麻哈鱼幼鱼每天浸入BVaraU水溶液(5微克/毫升,每天30分钟,共30次)中,并未延长受感染鱼的寿命。

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