Bernstein David I, Bravo Fernando J, Pullum Derek A, Shen Hui, Wang Mei, Rahman Aquilur, Glazer Robert I, Cardin Rhonda D
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Antivir Chem Chemother. 2015 Feb;24(1):19-27. doi: 10.1177/2040206614566581.
Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases.
The effects of N-methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated. For evaluation of recurrent infection, animals were treated for 21 days beginning 14 days after infection and disease recurrence and recurrent shedding were evaluated.
Treatment of the acute disease with N-methanocarbathymidine significantly reduced the severity of acute disease and decreased acute vaginal virus shedding more effectively than acyclovir. Significantly, none of the animals developed visible disease in the high-dose N-methanocarbathymidine group and this was the only group in which the number of days with recurrent virus shedding was reduced. Treatment of recurrent disease was equivalent to acyclovir when acyclovir was continuously supplied in the drinking water.
N-methanocarbathymidine was effective as therapy for acute and recurrent genital HSV-2 disease in the guinea pig models.
目前已获批用于治疗单纯疱疹病毒（HSV）生殖器感染的核苷疗法有效，但仍需要改进疗法来治疗急性和复发性疾病。
使用急性和复发性感染的豚鼠模型评估N-甲氧基碳胸苷的效果，并与阿昔洛韦进行比较。对于经阴道接种10(6)pfu HSV-2（MS株）后的急性疾病，动物在感染后24小时开始腹腔注射给药，并评估其对疾病严重程度、阴道病毒复制、随后的复发以及潜伏病毒载量的影响。为了评估复发性感染，动物在感染后14天开始接受21天的治疗，并评估疾病复发和复发排毒情况。
用N-甲氧基碳胸苷治疗急性疾病比阿昔洛韦更显著地降低了急性疾病的严重程度，并更有效地减少了急性阴道病毒排毒。值得注意的是，高剂量N-甲氧基碳胸苷组中没有动物出现明显疾病，并且这是唯一一组复发病毒排毒天数减少的组。当饮用水中持续供应阿昔洛韦时，复发性疾病的治疗效果与阿昔洛韦相当。
在豚鼠模型中，N-甲氧基碳胸苷作为急性和复发性生殖器HSV-2疾病的治疗方法有效。
