ANTIHERPESVIRUS ACTIVITY OF 9-(4-HYDROXY-3-HYDROXYMETHYLBUT-1-YL) GUANINE (BRL-39123) IN ANIMALS
ANTIHERPESVIRUS ACTIVITY OF 9-(4-HYDROXY-3-HYDROXYMETHYLBUT-1-YL) GUANINE (BRL-39123) IN ANIMALS
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DOI：
10.1128/aac.32.3.358
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发表时间：
1988-03-01
影响因子：
4.9
通讯作者：
SUTTON, D
中科院分区：
文献类型：
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作者：
BOYD, MR;BACON, TH;SUTTON, D
在几种单纯疱疹病毒（HSV）感染的动物模型中评估了9-（4-羟基-3-羟甲基丁-1-基）鸟嘌呤（BRL 39123）的抗病毒活性。BRL 39123局部应用于皮肤HSV 1型（HSV-1）感染的豚鼠时，其活性与阿昔洛韦（ACV）相同，局部应用于HSV-2生殖器感染时也具有活性。在对感染动物全身给药前，将BRL 39123和ACV经口和皮下给予小鼠，并通过高压液相色谱法测定血液中的每种化合物。当对HSV-1感染的小鼠全身给药时，BRL 39123与ACV一样具有活性。在鼻内感染HSV-1或HSV-2的小鼠中，BRL 39123每日单次皮下给药比ACV等效治疗更有效，反映了在细胞培养中观察到的更持久的活性和感染细胞内更稳定的三磷酸盐。当这些化合物在饮用水中用于这种感染时，BRL 39123和ACV对HSV-1具有相似的效力，尽管ACV对HSV-2感染的活性比BRL 39123更强。在腹腔内感染HSV-1的小鼠中，BRL 39123的效力是ACV的10倍，并且在感染后1、5和20 h给予单剂量BRL 39123比3剂量ACV更有效地减少腹腔内的病毒复制。尽管BRL 39123未能从潜伏感染HSV-1的小鼠中根除病毒，但在耳廓感染后5 h开始治疗可减少发生潜伏感染的小鼠数量。
The antiviral activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) was assessed in several animal models of herpes simplex virus (HSV) infection. BRL 39123 was as active as acyclovir (ACV) when applied topically to guinea pigs with a cutaneous HSV type 1 (HSV-1) infection and was also active topically in an HSV-2 genital infection. Before systemic administration to infected animals, BRL 39123 and ACV were administered orally and subcutaneously to mice, and the blood was assayed for each compound by high-pressure liquid chromatography. When given systemically to mice infected cutaneously with HSV-1, BRL 39123 was as active as ACV. In mice infected intranasally with HSV-1 or HSV-2, single daily subcutaneous doses of BRL 39123 were more effective than equivalent treatment with ACV, reflecting the more persistent activity seen in cell culture and a more stable triphosphate within the infected cell. When the compounds were supplied in drinking water for this infection, BRL 39123 and ACV had similar potencies against HSV-1, although ACV was more active against an HSV-2 infection than BRL 39123 was. In mice infected intraperitoneally with HSV-1, BRL 39123 was 10-fold more potent than ACV and a single dose of BRL 39123 reduced virus replication within the peritoneal cavity more effectively than 3 doses of ACV given 1, 5, and 20 h after infection. Although BRL 39123 failed to eradicate the virus from mice latently infected with HSV-1, treatment initiated 5 h after infection of the ear pinna reduced the numbers of mice that developed latent infections.