MODE OF ACTION OF RIBAVIRIN - EFFECT OF NUCLEOTIDE POOL ALTERATIONS ON INFLUENZA-VIRUS RIBONUCLEOPROTEIN SYNTHESIS
MODE OF ACTION OF RIBAVIRIN - EFFECT OF NUCLEOTIDE POOL ALTERATIONS ON INFLUENZA-VIRUS RIBONUCLEOPROTEIN SYNTHESIS
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DOI：
10.1016/0166-3542(85)90012-9
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发表时间：
1985-01-01
影响因子：
7.6
通讯作者：
KNIGHT, V
中科院分区：
文献类型：
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作者：
WRAY, SK;GILBERT, BE;KNIGHT, V
利巴韦林是一种鸟苷类似物，是一种广谱抗病毒药物，可有效治疗流感。在这项研究中，利巴韦林对流感病毒核糖核蛋白（RNP）的合成和核苷酸池大小的影响，同时测量。如通过UTP掺入所测量的，利巴韦林（100 μ M）使病毒RNP合成减少94%。通过高效液相色谱法测量的细胞内GTP池减少了约10%。45%，而其他核苷酸保持接近对照值。通过加入外源鸟苷（50 μ M）来逆转利巴韦林对病毒RNP合成的抑制作用的尝试导致病毒RNP合成仅部分恢复，尽管GTP库完全恢复。剂量-反应实验表明，在25 μ M利巴韦林时，GTP库显著减少（对照的65%），并且增加药物浓度仅引起GTP库的进一步少量减少（在100 μ M时为5-10%）。RNP合成在25 μ M利巴韦林时被抑制50%，在100 μ M利巴韦林时进一步降低至对照的5%。因此，利巴韦林的抗病毒活性可能是由于GTP池大小的减少以及对病毒复制酶的直接作用。
Ribavirin, a guanosine analog, is a broad spectrum antiviral agent which is effective in the treatment of influenza. In this study, the effect of ribavirin on influenza virus ribonucleoprotein (RNP) synthesis and nucleotide pool sizes was simultaneously measured. Ribavirin (100 .mu.M) reduced viral RNP synthesis 94% as measured by UTP incorporation. Intracellular GTP pools, measured by high performance liquid chromatography, were reduced .apprx. 45% in ribavirin treated cells, while other nucleotides remained near control values. Attempts to reverse ribavirin''s inhibitory effects on viral RNP synthesis by addition of exogenous guanosine (50 .mu.M) resulted in only a partial restoration of viral RNP synthesis, despite full restoration of the GTP pool. Dose-response experiments indicated that the GTP pool was significantly reduced (65% of control) at 25 .mu.M ribavirin, and increasing concentrations of the drug caused only a small further reduction in the GTP pool (5-10% at 100 .mu.M). RNP synthesis was inhibited by 50% at 25 .mu.M ribavirin and was further decreased to 5% of control at 100 .mu.M ribavirin. Thus, ribavirin''s antiviral activity may result from a reduction of the GTP pool size combined with direct effects on viral replicative enzymes.