The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase
The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase
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DOI：
10.1128/jvi.79.3.1943-1947.2005
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Neyts, J
中科院分区：
文献类型：
--
作者：
Leyssen, P;Balzarini, J;Neyts, J
目前尚不清楚细胞内GTP池的耗尽在多大程度上有助于利巴韦林的抗病毒活性。因此，(I)利巴韦林，(Ii)其5-乙炔类似物，5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide(EICAR)，和(Iii)霉酚酸(MPA)(一种化合物。仅抑制细胞内IMP脱氢酶活性)对黄病毒和副粘病毒的复制进行了研究。此外，这三种化合物对细胞内GTP池的影响也被评估。在广泛的浓度范围内，利巴韦林、EICAR和MPA的抗病毒活性与这些化合物对GTP池耗尽的影响之间观察到了线性关系。当将利巴韦林、EICAR和MPA抗病毒活性的50%有效浓度(EC(50)S)与相应的GTP池耗尽的EC_(50)值进行比较时，计算出线性相关关系。这些数据提供了令人信服的证据，证明利巴韦林体外抗黄病毒和副粘病毒的主要作用机制是基于对细胞IMP脱氢酶活性的抑制。
It is not yet clear to what extent depletion of intracellular GTP pools contributes to the antiviral activity of ribavirin. Therefore, the antiviral activities of (i) ribavirin, (ii) its 5-ethynyl analogue, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), and (iii) mycophenolic acid (MPA) (a compound that. inhibits only cellular IMP dehydrogenase activity) were studied on the replication of flaviviruses and paramyxoviruses. In addition, the effects of these three compounds on intracellular GTP pools were assessed. A linear correlation was observed over a broad concentration range between the antiviral activities of ribavirin, EICAR, and MPA and the effects of these compounds on GTP pool depletion. When the 50% effective concentrations (EC(50)s) for the antiviral activities of ribavirin, EICAR, and MPA were plotted against the respective EC50 values for GTP pool depletion, a linear correlation was calculated. These data provide compelling evidence that the predominant mechanism of action of ribavirin in vitro against flavi- and paramyxoviruses is based on inhibition of cellular IMP dehydrogenase activity.