Metabolism and antiviral activity of ribavirin
Metabolism and antiviral activity of ribavirin
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DOI：
10.1016/j.virusres.2004.11.006
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发表时间：
2005-02-01
期刊：
影响因子：
5
通讯作者：
Parker, WB
中科院分区：
文献类型：
--
作者：
Parker, WB
在其合成30年后，利巴韦林的作用机制仍然没有完全了解。虽然对利巴韦林在人体细胞中的代谢和生化作用已经了解很多，但关于利巴韦林与各种病毒的确切作用机制仍有很多需要了解。关于其诱导病毒基因组突变能力的新信息导致了关于其作用机制的新问题。有相当多的证据表明三磷酸利巴韦林（RTP）可以与各种病毒RNA聚合酶相互作用，这种相互作用似乎对利巴韦林的作用机制很重要。利巴韦林似乎不会有一个通用的作用机制，但会以不同的方式抑制不同的病毒。在某些情况下，IMP脱氢酶的抑制可能足以产生抗病毒活性。然而，在其他情况下，RTP对病毒RNA聚合酶的抑制可能更重要。RTP也可能以不同的方式与不同的病毒RNA聚合酶相互作用，导致不同的作用机制。需要更全面的研究，解决利巴韦林代谢和生化作用的各个方面，以获得对这种代理商的活动的透彻理解。最后，利巴韦林、硒唑弗林和硫唑弗林的代谢和生化作用的差异表明，微小的结构变化可能对生物活性产生深远的影响。这一观察结果是熟悉核苷类似物的研究人员所熟知的，但表明不应假定类似结构的药物具有相同的活性。(C)2004 Elsevier B.V.保留所有权利。
Thirty years after its synthesis, the mechanism of action of ribavirin is still not completely understood. Although much is known about the metabolism and biochemical effects of ribavirin in human cells, there is still much to be learned about the precise mechanism of action of ribavirin with the various viruses. New information about its ability to induce mutations in viral genomes has led to new questions about its mechanism of action. There is considerable evidence that indicates that ribavirin triphosphate (RTP) can interact with the various viral RNA polymerases, and it seems likely that this interaction is important to the mechanism of action of ribavirin. It seems likely that ribavirin will not have one universal mechanism of action, but will inhibit different viruses in different ways. In some cases, inhibition of IMP dehydrogenase may be sufficient for antiviral activity. Whereas, in other cases, inhibition of viral RNA polymerases by RTP may be more important. It is also likely that RTP will interact with the different viral RNA polymerases in different ways leading to different mechanisms of actions. More comprehensive studies are needed that address all aspects of ribavirin metabolism and biochemical actions to gain a thorough understanding of the activity of this agent. Finally, the differences in the metabolism and biochemical actions of ribavirin, selenazofurin, and tiazofurin indicate that small structural changes can have profound effects on biological activity. This observation is well known by investigators familiar with nucleoside analogs, but indicate that one should not assume that agents of similar structure have identical activities.(C) 2004 Elsevier B.V. All rights reserved.