de Oliveira C B, Stevenson D, LaBree L, McDonnell P J, Trousdale M D
Doheny Eye Institute, Department of Ophthalmology, University of Southern California School of Medicine, Los Angeles, CA 900033, USA.
Antiviral Res. 1996 Jul;31(3):165-72. doi: 10.1016/0166-3542(95)00962-0.
The antiviral inhibitory activity of Cidofovir [1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate, HPMPC, GS-504] against adenovirus type 5 (Ad5) in the New Zealand rabbit ocular replication model was evaluated. The 50% inhibitory dose (ID50) of Cidofovir was determined to be 4.7-9.5 micrograms/ml against four adenoviruses (two Ad5, Ad8 and Ad14) by plaque reduction assay in A549 cells. Twenty-four New Zealand rabbits received intrastromal inoculation and topical application of 2 x 10(6) plaque-forming units (PFU) per eye of Ad5 McEwen, a clinical isolate. Cidofovir was administered topically at three different concentrations twice per day, beginning 16 h postinoculation and continuing for 20 consecutive days. The inhibitory effects were determined by measuring suppression of virus replication and by observation of the clinical effects. Compared to the placebo group, the 1% and 0.5% Cidofovir-treated groups showed significantly reduced Ad5 ocular titers, fewer days of viral shedding and less severe subepithelial opacities (P = 0.0001). The 1% Cidofovir group had the lowest humoral antibody titer against adenovirus antigens, but the difference was not significant (P = 0.24). Cidofovir proved to have potent antiviral activity against adenovirus replication and may have great promise for the treatment of adenovirus infection. Further investigation is recommended.
评估了西多福韦[1-[(S)-3-羟基-2-(膦酰甲氧基)丙基]胞嘧啶二水合物，HPMPC，GS-504]在新西兰兔眼内复制模型中对5型腺病毒（Ad5）的抗病毒抑制活性。通过在A549细胞中进行蚀斑减少试验，确定西多福韦对四种腺病毒（两种Ad5、Ad8和Ad14）的50%抑制剂量（ID50）为4.7-9.5微克/毫升。24只新西兰兔接受了基质内接种，并每只眼局部应用2×10⁶蚀斑形成单位（PFU）的临床分离株Ad5 McEwen。接种后16小时开始，每天两次以三种不同浓度局部给予西多福韦，并连续持续20天。通过测量病毒复制的抑制情况和观察临床效果来确定抑制作用。与安慰剂组相比，1%和0.5%西多福韦治疗组的Ad5眼内滴度显著降低，病毒脱落天数减少，上皮下混浊程度减轻（P = 0.0001）。1%西多福韦组针对腺病毒抗原的体液抗体滴度最低，但差异不显著（P = 0.24）。西多福韦被证明对腺病毒复制具有强大的抗病毒活性，可能对腺病毒感染的治疗有很大前景。建议进一步研究。
