EFFECT OF A NOVEL ADENOSINE DEAMINASE INHIBITOR (CO‐VIDARABINE, CO‐V) UPON THE ANTIVIRAL ACTIVITY IN VITRO AND IN VIVO OF VIDARABINE (VIRA‐ATM) FOR DNA VIRUS REPLICATION
EFFECT OF A NOVEL ADENOSINE DEAMINASE INHIBITOR (CO‐VIDARABINE, CO‐V) UPON THE ANTIVIRAL ACTIVITY IN VITRO AND IN VIVO OF VIDARABINE (VIRA‐ATM) FOR DNA VIRUS REPLICATION
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DOI：
10.1111/j.1749-6632.1977.tb21937.x
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发表时间：
1977-05
影响因子：
5.2
通讯作者：
B. Sloan;J. K. Kielty;F. Miller
中科院分区：
文献类型：
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作者：
B. Sloan;J. K. Kielty;F. Miller
在与阿糖腺苷(Vidarabine，Vira-ATM)的联合研究中，一种新的有效的腺苷脱氨酶抑制剂(co-Vidarabine)被用来保护这种嘌呤核苷不受酶促脱氨作用的影响，从而保护更弱的代谢产物次黄嘌呤阿拉伯糖苷。与单用阿达拉滨相比，在组织培养和皮下观察到联合用药对疱疹病毒和痘苗病毒的抗病毒活性显著提高(10倍)，对小鼠颅脑疱疹病毒感染的抗病毒活性也显著提高。其他几名研究人员最近也报告了新描述的脱氨酶抑制剂使阿达拉滨的活性提高了几倍。他们观察到，与单独使用阿达拉滨相比，几种含有DNA的大型病毒(疱疹、牛痘、水痘带状疱疹)和含有RNA的致癌病毒形成的斑块被联合使用显著防止。在动物方面，也观察到与单独使用阿达拉滨相比，使用两种药物组合治疗的垂死小鼠的保护作用得到增强(幸存者增加)和/或死亡小鼠的寿命显著延长。这些在动物身上的观察清楚地表明，与长春瑞滨(Vira-ATM)和联合长春瑞滨(脱氨酶抑制剂)的联合研究值得认真考虑，作为包括疱疹病毒性脑炎在内的人类全身病毒感染的未来治疗方法。
A new potent inhibitor of adenosine deaminase (co-vidarabine) was used in combination studies with adenine arabinoside (vidarabine, Vira-ATM) to protect this purine nucleoside from enzymatic deamination to the more weakly active metabolite, hypoxanthine arabinoside. Comparing the combination to vidarabine alone, a significant increase (10-fold) of the antiviral activity of the combined drugs was observed against herpes and vaccinia viruses in tissue culture and subcutaneously, against cranial herpesvirus infections in mice. Several other investigators have also recently reported several-fold enhancement of vidarabine activity by newly described deaminase inhibitors. They observed that plaque formation by several large DNA-containing viruses (herpes, vaccinia, varicella zoster) and an RNA-containing oncogenic virus was markedly prevented by the combination compared to vidarabine alone. In animals, enhanced protection (increased survivors) and/or highly significant increase in the life span of dying mice treated with the 2-drug combination, was also observed compared to vidarabine administered singly. These observations in animals clearly indicate that combination studies with vidarabine (Vira-ATM) and co-vidarabine (deaminase inhibitor) deserve serious consideration as future therapy for systemic virus infections in man including herpesvirus encephalitis.