Kern E R, Richards J T, Overall J C, Glasgow L A
Antiviral Res. 1981 Nov;1(4):225-35. doi: 10.1016/0166-3542(81)90013-9.
The activity of phosphonoacetic acid (PAA) and phosphonoformic acid (PFA) against four strains of herpes simplex virus type 1 (HSV-1) and four strains of HSV-2 were compared in tissue culture and in a murine model of genital herpes. In mouse embryo fibroblast cells, both drugs were three-fold more active against the HSV-1 strains than against the HSV-2 strains. In contrast, in the animal model infections, PAA appeared to be more active against the HSV-2 strains, while PFA was equally effective against both HSV types. In mice infected intravaginally with HSV-2 and treated with intravaginal 5% PAA, none of the treated mice became infected, replication of virus in the genital tract was completely inhibited, none of the infected mice died from encephalitis, and latent infection in lumbosacral ganglia of surviving animals was completely prevented. In HSV-1 genital infection treated with PAA, 20-60% of mice became infected, replication of virus in the genital tract was strikingly reduced, none of the infected mice died, and latent infection was completely prevented. In both HSV-2 and HSV-1 genital infections, 20-70% of animals treated with 8% PFA became infected, growth of virus in the genital tract was reduced significantly but not completely suppressed, mortality was variably altered, and there was a trend towards reduction in the frequently of latent infection. These results indicate that HSV-1 strains are more sensitive to PAA and PFA in tissue culture, but the HSV-2 strains are generally more amenable to therapy in the murine model of genital herpes. Although PAA appeared to be more active that PFA in the genital infection, both drugs significantly altered the course of the infection. Since dermal toxicity associated with PAA precludes its use in humans and since PFA is already undergoing trials in patients with recurrent herpes labialis, the current results suggest that topical PFA deserved further evaluation in the treatment of mucocutaneous HSV infections, including genital herpes.
在组织培养和生殖器疱疹小鼠模型中，比较了膦乙酸（PAA）和膦甲酸（PFA）对四株1型单纯疱疹病毒（HSV-1）和四株2型单纯疱疹病毒（HSV-2）的活性。在小鼠胚胎成纤维细胞中，两种药物对HSV-1毒株的活性比对HSV-2毒株的活性高两倍。相反，在动物模型感染中，PAA对HSV-2毒株似乎更具活性，而PFA对两种HSV类型同样有效。在用HSV-2阴道内感染并经阴道给予5%PAA治疗的小鼠中，没有一只治疗小鼠被感染，生殖道中的病毒复制被完全抑制，没有一只感染小鼠死于脑炎，存活动物腰骶神经节中的潜伏感染也被完全预防。在用PAA治疗的HSV-1生殖器感染中，20%-60%的小鼠被感染，生殖道中的病毒复制显著减少，没有一只感染小鼠死亡，潜伏感染也被完全预防。在HSV-2和HSV-1生殖器感染中，用8%PFA治疗的动物中有20%-70%被感染，生殖道中病毒的生长显著减少但未被完全抑制，死亡率有不同变化，潜伏感染的频率有降低趋势。这些结果表明，HSV-1毒株在组织培养中对PAA和PFA更敏感，但HSV-2毒株在生殖器疱疹小鼠模型中通常对治疗更敏感。尽管在生殖器感染中PAA似乎比PFA更具活性，但两种药物都显著改变了感染进程。由于与PAA相关的皮肤毒性使其无法用于人类，且PFA已在复发性唇疱疹患者中进行试验，目前的结果表明，局部应用PFA在治疗包括生殖器疱疹在内的黏膜皮肤HSV感染方面值得进一步评估。
