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E-5-(2-溴乙烯基)-1-β-D-阿拉伯呋喃糖基尿嘧啶对单纯疱疹病毒复制及DNA合成的抑制作用

Inhibitory effect of E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil on herpes simplex virus replication and DNA synthesis.

作者信息

Descamps J, Sehgal R K, De Clercq E, Allaudeen H S

出版信息

J Virol. 1982 Jul;43(1):332-6. doi: 10.1128/JVI.43.1.332-336.1982.

Abstract

The effect of E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) on herpes simplex virus (HSV) replication was examined and compared with that of E-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd). The 50% inhibitory dose against HSV type 1 (HSV-1) was 0.1 microgram/ml compared with 0.008 microgram/ml for BVdUrd; the antimetabolic 50% inhibitory dose of BVaraU ranged from 20 to 95 micrograms/ml. The addition of 50 micrograms of BVaraU per ml to HSV-1-infected Vero cells decreased the synthesis of viral and cellular DNA by 37 and 28%, respectively. The 5'-triphosphate (BVaraUTP) competed with dTTP in DNA synthesis by the herpes-viral and cellular DNA polymerases; the apparent Ki values of HSV-1 DNA polymerase, DNA polymerase alpha, and DNA polymerase beta were 0.14, 0.32, and 5 microM, respectively. Thus, BVaraU was a less effective antiherpesvirus agent than BVdUrd; unlike BVdUrd, it did not appear to be internally incorporated into replicating DNA in virus-infected cells.

摘要

研究了E-5-(2-溴乙烯基)-1-β-D-阿拉伯呋喃糖基尿嘧啶(BVaraU)对单纯疱疹病毒(HSV)复制的影响,并与E-5-(2-溴乙烯基)-2'-脱氧尿苷(BVdUrd)进行了比较。对1型单纯疱疹病毒(HSV-1)的50%抑制剂量为0.1微克/毫升,而BVdUrd为0.008微克/毫升;BVaraU的抗代谢50%抑制剂量范围为20至95微克/毫升。每毫升向感染HSV-1的Vero细胞中添加50微克BVaraU,可使病毒DNA和细胞DNA的合成分别减少37%和28%。5'-三磷酸(BVaraUTP)在疱疹病毒和细胞DNA聚合酶的DNA合成中与dTTP竞争;HSV-1 DNA聚合酶、DNA聚合酶α和DNA聚合酶β的表观Ki值分别为0.14、0.32和5微摩尔。因此,BVaraU是一种比BVdUrd效果更差的抗疱疹病毒药物;与BVdUrd不同,它似乎没有在病毒感染的细胞中内在地掺入复制的DNA中。

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