Inhibition of Epstein-Barr virus replication by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.
Inhibition of Epstein-Barr virus replication by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil.
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新型 L-核苷 2-氟-5-甲基-β-L-阿拉伯呋喃糖尿嘧啶抑制 Epstein-Barr 病毒复制。
DOI：
10.1016/0006-2952(96)00049-4
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发表时间：
1996
影响因子：
5.8
通讯作者：
Cheng,YC
中科院分区：
文献类型：
--
作者：
Yao,GQ;Liu,SH;Chou,E;Kukhanova,M;Chu,CK;Cheng,YC
新的L-核苷类似物2′-氟-5-甲基-β-L-阿拉伯呋喃糖基尿嘧啶（l-FMAU）是一种有效的、选择性的EB病毒（EBV）复制抑制剂。病毒产量的减少具有浓度依赖性，90%抑制浓度约为5 μM。从处理的细胞中去除药物后，病毒生产在21天内恢复。代谢研究表明，l-FMAU可以在EBV产生和非产生细胞中转化为其单磷酸、二磷酸和三磷酸代谢物。然而，在EBV产生细胞中形成的I-FMAU核苷酸的量是在EBV非产生细胞中形成的I-FMAU核苷酸的量的三倍。I-FMAU对EBV的选择性机制似乎不仅仅是由于I-FMAU在EBV产生细胞中的优先磷酸化。I-FMAU的三磷酸不能被EBV DNA聚合酶或人DNA聚合酶α、β、γ或δ用作底物。因此，I-FMAU残基掺入病毒DNA可能不是抗病毒活性的机制。该化合物似乎具有不同于任何其他抗疱疹病毒核苷类似物的作用机制。此外，l-FMAU具有非常低的细胞毒性，在1 mM的浓度下发生50%的细胞生长抑制。鉴于该化合物对EBV的有效抑制活性及其不能掺入细胞DNA，l-FMAU类似物应被探索为一类新的抗EBV药物。
A novel l-nucleoside analog, 2′-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-FMAU), was found to be a potent and selective inhibitor of Epstein-Barr virus (EBV) replication. The decrease in the amount of viral production was concentration dependent with a 90% inhibitory concentration of approximately 5 μM. Upon removal of the drug from treated cells, virus production resumed in 21 days. Metabolism studies indicated that l-FMAU could be converted to its mono-, di- and triphosphate metabolites in both EBV producing and non-producing cells. However, the amount of l-FMAU nucleotides formed was three times larger in EBV producing cells than in EBV non-producing cells. The mechanism of selectivity of l-FMAU against EBV does not appear to be due solely to the preferential phosphorylation of l-FMAU in EBV producing cells. The triphosphate of l-FMAU could not be utilized as a substrate by EBV DNA polymerase or the human DNA polymerases α, β, γ, or δ. Therefore, the incorporation of l-FMAU residues into viral DNA may not be the mechanism of antiviral activity. This compound appears to have a mechanism of action different from that of any other antiherpes virus nucleoside analogs. In addition, l-FMAU has very low cytotoxicity with 50% inhibition of cell growth occurring at a concentration of 1 mM. Given the potent inhibitory activity of this compound against EBV and its inability to be incorporated into cellular DNA, l-FMAU analogs should be explored as a new class of anti-EBV agents.
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阿昔洛韦治疗疱疹病毒感染
DOI：
--
发表时间：
1990
期刊：
影响因子：
--
作者：
D. Baker
通讯作者：
D. Baker
9-(1,3-二羟基-2-丙氧基甲基)鸟嘌呤对八名免疫抑制的同性恋男性严重巨细胞病毒病的影响。
影响因子：
39.2
作者：
Henry Masur;H. Lane;Alan G. Palestine;Phillip D. Smith;J. Manischewitz;Garth Stevens;Leslie S. Fujikawa;Abe M. Macher;R. Nussenblatt;B. Baird;Margaret Megill;A. E. Wittek;G. Quinnan;J. Parrillo;Alain H. Rook;L. J. Eron;D. Poretz;Robin I. Goldenberg;A. Fauci;E. Gelmann
通讯作者：
E. Gelmann
临床标本中 Epstein-Barr 病毒的检测和表征。
影响因子：
6
作者：
R. Ambinder;R. Mann
通讯作者：
R. Mann
NIH、PDA 从乙型肝炎药物试验死亡中吸取教训
影响因子：
64.8
作者：
C. Macilwain
通讯作者：
C. Macilwain
DOI：
10.1073/pnas.80.9.2767
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHENG, YC;HUANG, ES;GRILL, SP
通讯作者：
GRILL, SP