Iwayama S, Ohmura Y, Suzuki K, Ono N, Nakazawa H, Aoki M, Tanabe I, Sekiyama T, Tsuji T, Okunishi M, Yamanishi K, Nishiyama Y
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Antiviral Res. 1999 Jun;42(2):139-48. doi: 10.1016/s0166-3542(99)00024-8.
The anti-herpesvirus activity of (1'S,2'R)-9-[[1',2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guani ne (A-5021) was evaluated in murine cells and in several murine models of herpes simplex virus (HSV) infection. Against HSV type 1 (HSV-1), A-5021 was 15-30- and 30-60-fold more active, and against HSV type 2 (HSV-2), it was 2- and 8-fold more active than acyclovir and penciclovir in Balb/3T3 cells, respectively. When antiviral compounds were administered orally (once daily) to mice infected intraperitoneally with HSV-1 (Tomioka), A-5021 was more active than acyclovir or famciclovir in spite of its relatively low oral bioavailability. A-5021 was as active as penciclovir when the antiviral compounds were given intravenously (three times daily) to mice infected intraperitoneally with HSV-2 (186). In mice with a cutaneous HSV-1 (KOS) infection, three times daily oral therapy with A-5021 at 25 mg/kg per day produced more significant reduction in severity of skin lesions than equivalent treatment with acyclovir or famciclovir. In mice infected intracerebrally with HSV-1 (Tomioka), complete survival was observed in the group treated intravenously with A-5021 at 25 mg/kg per day (three times daily), while more than 50% of mice died in the groups treated intravenously with acyclovir of up to 100 mg/kg per day (three times daily). Moreover, A-5021 was more effective than acyclovir in clearing infectious virus from the brain. These findings demonstrate that A-5021 has potent anti-HSV activity in several murine models.
在鼠细胞以及单纯疱疹病毒（HSV）感染的多种鼠模型中评估了（1'S,2'R）-9-[[1',2'-双（羟甲基）环丙-1'-基]甲基]鸟嘌呤（A-5021）的抗疱疹病毒活性。在Balb/3T3细胞中，A-5021对1型单纯疱疹病毒（HSV-1）的活性分别比阿昔洛韦和喷昔洛韦高15 - 30倍和30 - 60倍，对2型单纯疱疹病毒（HSV-2）的活性分别比它们高2倍和8倍。当给经腹腔感染HSV-1（富冈株）的小鼠口服（每日一次）抗病毒化合物时，尽管A-5021的口服生物利用度相对较低，但它比阿昔洛韦或泛昔洛韦更具活性。当给经腹腔感染HSV-2（186株）的小鼠静脉注射（每日三次）抗病毒化合物时，A-5021与喷昔洛韦活性相当。在患有皮肤HSV-1（KOS株）感染的小鼠中，每天以25mg/kg的剂量对A-5021进行每日三次的口服治疗，与用阿昔洛韦或泛昔洛韦进行等效治疗相比，皮肤损伤严重程度的降低更为显著。在经脑内感染HSV-1（富冈株）的小鼠中，观察到每天以25mg/kg的剂量（每日三次）静脉注射A-5021的治疗组小鼠全部存活，而每天静脉注射高达100mg/kg（每日三次）阿昔洛韦的治疗组中有超过50%的小鼠死亡。此外，A-5021在清除脑内感染性病毒方面比阿昔洛韦更有效。这些发现表明，A-5021在多种鼠模型中具有强大的抗HSV活性。
