Mar E C, Chu C K, Lin J C
Tumor Virology Laboratory, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Antiviral Res. 1995 Sep;28(1):1-11. doi: 10.1016/0166-3542(95)92835-b.
The effects of (+)-beta-D-dioxolane-cytosine ((+)-D-beta-DOC), (-)-beta-L-dioxolane-cytosine ((-)-L-beta-DOC), (+)-beta-D-oxathiolane-cytosine ((+)-D-beta-OTC), (-)-beta-L-oxathiolane-cytosine ((-)-L-beta-OTC, or 3TC), 3'-azido-2',3'-dideoxy-5-methyl-cytidine (5-Me-AZDC), and 3'-azido-2',3'-dideoxyuridine (AZDU) on Epstein-Barr virus (EBV) DNA replication in vitro were tested in P3HR-1 cells. Two anti-EBV drugs, 3'-azido-3'-deoxythymidine (AZT) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG, or ganciclovir), were used as positive controls. The inhibitory effects on EBV DNA synthesis were quantified by membrane filter and Southern blot hybridizations with an EBV-specific probe BamHI-W fragment. The 50% effective doses (ED50) for EBV DNA replication were 0.15, 0.83, 1.5, 8.3, 14, and 7.7 microM for DHPG, (-)-L-beta-DOC, (+)-D-beta-DOC, (+)-D-beta-OTC, (-)-L-beta-OTC, and AZT, respectively. In contrast, 5-Me-AZDC and AZDU were not effective at concentrations as high as 30 microM. These results indicated that both (-)-L-beta-DOC and (+)-D-beta-DOC were more potent than AZT, which has previously been shown to have anti-EBV activity. (-)-L-beta-DOC and (+)-D-beta-DOC have also been previously demonstrated to suppress the infectivity of human immunodeficiency virus type 1 (HIV-1). Thus, (-)-L-beta-DOC represents the first nucleoside analog with L-configuration exhibiting significant antiviral activities against both EBV and HIV.
在P3HR - 1细胞中测试了（+）-β-D-二氧戊环胞嘧啶（（+）-D-β-DOC）、（-）-β-L-二氧戊环胞嘧啶（（-）-L-β-DOC）、（+）-β-D-氧硫杂环戊烷胞嘧啶（（+）-D-β-OTC）、（-）-β-L-氧硫杂环戊烷胞嘧啶（（-）-L-β-OTC，即3TC）、3'-叠氮基-2'，3'-二脱氧-5-甲基胞苷（5-Me-AZDC）和3'-叠氮基-2'，3'-二脱氧尿苷（AZDU）对体外Epstein-Barr病毒（EBV）DNA复制的影响。两种抗EBV药物，3'-叠氮基-3'-脱氧胸苷（AZT）和9-（1,3-二羟基-2-丙氧基甲基）鸟嘌呤（DHPG，即更昔洛韦）用作阳性对照。通过膜过滤和用EBV特异性探针BamHI-W片段进行Southern印迹杂交来定量对EBV DNA合成的抑制作用。对于EBV DNA复制，DHPG、（-）-L-β-DOC、（+）-D-β-DOC、（+）-D-β-OTC、（-）-L-β-OTC和AZT的50%有效剂量（ED50）分别为0.15、0.83、1.5、8.3、14和7.7 microM。相比之下，5-Me-AZDC和AZDU在高达30 microM的浓度下无效。这些结果表明，（-）-L-β-DOC和（+）-D-β-DOC都比AZT更有效，之前已证明AZT具有抗EBV活性。（-）-L-β-DOC和（+）-D-β-DOC之前也已被证明可抑制1型人类免疫缺陷病毒（HIV-1）的感染性。因此，（-）-L-β-DOC是第一种具有L构型且对EBV和HIV均表现出显著抗病毒活性的核苷类似物。
