Wray S K, Smith R H, Gilbert B E, Knight V
Antimicrob Agents Chemother. 1986 Jan;29(1):67-72. doi: 10.1128/AAC.29.1.67.
We studied the effects of selenazofurin alone and in combination with ribavirin on replication of influenza A and B viruses. These drugs showed little cytotoxicity as measured by leucine incorporation into protein in MDCK cells, although they were potent inhibitors of viral replication in the same cells. Selenazofurin inhibited growth of influenza A and B viruses at concentrations (50% inhibitory dose = 25 and 19 microM, respectively) which were similar to those at which growth was inhibited by ribavirin (50% inhibitory dose = 50 and 30 microM, respectively). The inhibition of replication of either influenza A or B virus was additive for any combination of ribavirin and selenazofurin. The effects of the 5'-triphosphate of selenazofurin on two replicative functions associated with the influenza virus RNA-dependent RNA polymerases, primer generation (initiation of transcription) and its subsequent elongation, were measured. Elongation was more sensitive to selenazofurin 5'-triphosphate than was primer generation, and the effects of this drug on these functions were approximately the same as those of ribavirin 5'-triphosphate. The activities of ribavirin triphosphate and selenazofurin triphosphate were additive, and combinations did not potentiate the individual inhibitory effects of these drugs on elongation.
我们研究了单独使用硒唑嘌呤以及将其与利巴韦林联合使用对甲型和乙型流感病毒复制的影响。通过测量亮氨酸掺入MDCK细胞蛋白质中的量来评估，这些药物显示出很小的细胞毒性，尽管它们是同一细胞中病毒复制的有效抑制剂。硒唑嘌呤在与利巴韦林抑制病毒生长的浓度（50%抑制剂量分别为25和19微摩尔）相似的浓度下（50%抑制剂量分别为25和19微摩尔）抑制甲型和乙型流感病毒的生长。对于利巴韦林和硒唑嘌呤的任何组合，甲型或乙型流感病毒复制的抑制作用都是相加的。测定了硒唑嘌呤5'-三磷酸对与流感病毒RNA依赖性RNA聚合酶相关的两种复制功能的影响，即引物生成（转录起始）及其随后的延伸。延伸对硒唑嘌呤5'-三磷酸比对引物生成更敏感，并且该药物对这些功能的影响与利巴韦林5'-三磷酸的影响大致相同。利巴韦林三磷酸和硒唑嘌呤三磷酸的活性是相加的，并且联合使用不会增强这些药物对延伸的单独抑制作用。
