ANTIVIRAL ACTIVITY OF ARABINOSYLADENINE AND ARABINOSYLHYPOXANTHINE IN HERPES-SIMPLEX VIRUS-INFECTED KB CELLS - SELECTIVE-INHIBITION OF VIRAL DEOXYRIBONUCLEIC-ACID SYNTHESIS IN PRESENCE OF AN ADENOSINE-DEAMINASE INHIBITOR
ANTIVIRAL ACTIVITY OF ARABINOSYLADENINE AND ARABINOSYLHYPOXANTHINE IN HERPES-SIMPLEX VIRUS-INFECTED KB CELLS - SELECTIVE-INHIBITION OF VIRAL DEOXYRIBONUCLEIC-ACID SYNTHESIS IN PRESENCE OF AN ADENOSINE-DEAMINASE INHIBITOR
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DOI：
10.1128/aac.10.1.64
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发表时间：
1976-01-01
影响因子：
4.9
通讯作者：
DRACH, JC
中科院分区：
文献类型：
--
作者：
SCHWARTZ, PM;SHIPMAN, C;DRACH, JC
假核苷arabinosyladenine （ara-A）对1型单纯疱疹病毒（HSV）的抗病毒活性被腺苷脱氨酶抑制剂coformycin提高了近20倍。ara-A + coformycin联合阻断HSV复制的效力是arabinosylhypoxanthine （ara-H）的90倍。两种药物在悬浮培养中均比在单层培养中活性更强。脱氧核糖核酸（DNA）的合成也受到核苷的抑制。根据所检测的DNA种类不同，ara-A在柯福霉素存在时的活性是ara-A的8到15倍，而其组合的效力是ara-H的35到70倍。两种药物在未感染和单纯疱疹病毒感染的KB细胞中抑制总DNA合成的程度相同。相比之下，病毒DNA合成比细胞DNA合成更容易受到抑制3到6倍。悬浮培养比单层培养对病毒DNA合成的抑制更明显。然而，细胞增殖的方法并没有改变药物抑制未感染KB细胞DNA合成的程度。已经衍生出一个指数来量化选择性抑制病毒或细胞DNA合成的程度。计算药物对未感染的KB DNA合成和病毒DNA合成的50%抑制浓度，并以比率表示。该比值的对数被称为选择指数，如果病毒DNA合成被优先抑制，则为正，如果未感染的KB DNA合成被更强烈地抑制，则为负。在单层培养中进行的实验数据显示，ara-A + coformycin、ara-A和ara-H的阳性选择指数分别为0.3、0.5和0.4。ara-A + coformycin和ara-H的悬浮培养数据分别为0.7和0.6。综合考虑，本通讯中提供的数据表明，科福霉素增加了ara-A的效力，但没有增加其选择性。
The antiviral activity of the fraudulent nucleoside arabinosyladenine (ara-A) against herpes simplex virus (HSV) type 1 was increased nearly 20-fold by the adenosine deaminase inhibitor, coformycin. The combination of ara-A plus coformycin was 90 times more potent in blocking HSV replication than was arabinosylhypoxanthine (ara-H). In suspension culture both drugs were more active than they were in monolayer culture. Deoxyribonucleic acid (DNA) synthesis also was inhibited by the nucleosides. Depending upon the species of DNA examined, ara-A was 8 to 15 times more active in the presence of coformycin, and the combination was 35 to 70 times more potent than ara-H. Both drugs inhibited total DNA synthesis to the same extent in uninfected and HSV-infected KB cells. In contrast, viral DNA synthesis was three to six times more susceptible to inhibition than was cellular DNA synthesis. Inhibition of viral DNA synthesis was more pronounced in suspension culture than in monolayer culture. However, the method of cell propagation did not alter the degree to which the drugs inhibited DNA synthesis in uninfected KB cells. An index has been derived to quantitate the extent of the selective inhibition of viral or cellular DNA synthesis. Fifty percent inhibitory concentrations of a drug were calculated for uninfected KB DNA synthesis and viral DNA synthesis and expressed as a ratio. The logarithm of this ratio was termed the selective index and was positive if viral DNA synthesis was inhibited preferentially or negative if uninfected KB DNA synthesis was more strongly inhibited. Data from experiments performed in monolayer culture gave positive selective index values of 0.3, 0.5, and 0.4 for ara-A plus coformycin, ara-A, and ara-H, respectively. Values of 0.7 and 0.6 were obtained from suspension culture data for ara-A plus coformycin and ara-H, respectively. Considered collectively, the data presented in this communication establish that coformycin increased the potency of ara-A but did not increase its selectivity.