The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen
The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen
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DOI：
10.1038/82191
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发表时间：
2000-12-01
期刊：
影响因子：
82.9
通讯作者：
Cameron, CE
中科院分区：
文献类型：
--
作者：
Crotty, S;Maag, D;Cameron, CE
核糖核苷类似物利巴韦林（1-β-D-呋喃核糖基-1，2，4-三唑-3-甲酰胺）显示出抗多种RNA病毒的抗病毒活性，并与干扰素-α联合用于治疗丙型肝炎病毒感染。在这里，我们显示了在体外使用利巴韦林三磷酸的模型病毒RNA聚合酶，脊髓灰质炎病毒3D（波尔）。利巴韦林掺入具有致突变性，因为它以相同的效率模板掺入胞苷和尿苷。利巴韦林可将细胞培养物中的感染性脊髓灰质炎病毒产量降低至0.00001%。利巴韦林的抗病毒活性与其致突变活性直接相关。这些数据表明，利巴韦林迫使病毒进入“错误灾难”。因此，诱变核糖核苷可能代表一类重要的抗RNA病毒剂。
The ribonucleoside analog ribavirin (1-beta -D-ribofuranosyl-1,2,4-triazole-3-carboxamide) shows antiviral activity against a variety of RNA viruses and is used in combination with interferon-alpha to treat hepatitis C virus infection. Here we show in vitro use of ribavirin triphosphate by a model viral RNA polymerase, poliovirus 3D(pol). Ribavirin incorporation is mutagenic, as it templates incorporation of cytidine and uridine with equal efficiency. Ribavirin reduces infectious poliovirus production to as little as 0.00001% in cell culture. The antiviral activity of ribavirin correlates directly with its mutagenic activity. These data indicate that ribavirin forces the virus into 'error catastrophe'. Thus, mutagenic ribonucleosides may represent an important class of anti-RNA virus agents.