Lobe D C, Spector T, Ellis M N
Division of Virology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Antiviral Res. 1991 Feb;15(2):87-100. doi: 10.1016/0166-3542(91)90027-o.
Combination therapy with A1110U, an inactivator of the herpes simplex virus (HSV) and the varicella zoster virus ribonucleotide reductase, and acyclovir (ACV) was evaluated for treatment of cutaneous herpetic disease in athymic mice infected on the dorsum. In this model, infection with HSV produces a 'zosteriform-like' rash that is first visible on day 3 or 4 post-infection (p.i.) and eventually extends from the anterior mid-line to the dorsal mid-line of the affected flank. In untreated mice, the infection is fatal at about day 7 p.i. presumably due to central nervous system involvement. Topical treatment of infections induced by either wild-type (wt) HSV-1 or wt HSV-2 with 3% A1110U in combination with 5% ACV resulted in synergistic (P less than 0.01) reductions in lesion scores. Therapy was also synergistic in mice infected with an ACV-resistant thymidine kinase-deficient mutant and an ACV-resistant TK-altered mutant HSV-1 isolated. Combination therapy was very effective in reducing lesion scores of mice infected with an ACV-resistant HSV-1 DNA polymerase mutant, but did not result in statistically significant synergy (P = 0.07) because of the enhanced efficacy of A1110U alone against this virus. These results provide encouragement that the combination of A1110U and ACV may offer an effective therapy for topical treatment of cutaneous HSV infections in humans.
对携带单纯疱疹病毒（HSV）和水痘带状疱疹病毒核糖核苷酸还原酶失活剂A1110U与阿昔洛韦（ACV）的联合疗法进行了评估，用于治疗背部感染的无胸腺小鼠的皮肤疱疹疾病。在该模型中，HSV感染产生一种“带状疱疹样”皮疹，在感染后（p.i.）第3天或第4天首次可见，最终从受影响侧翼的前中线延伸至背中线。在未治疗的小鼠中，感染在感染后约第7天致死，可能是由于中枢神经系统受累。用3%A1110U与5%ACV联合局部治疗由野生型（wt）HSV-1或wt HSV-2引起的感染，导致病变评分协同降低（P小于0.01）。该疗法对感染ACV耐药的胸苷激酶缺陷突变体和分离出的ACV耐药的TK改变突变体HSV-1的小鼠也具有协同作用。联合疗法在降低感染ACV耐药HSV-1 DNA聚合酶突变体的小鼠病变评分方面非常有效，但由于A1110U单独对该病毒的疗效增强，未产生统计学上显著的协同作用（P = 0.07）。这些结果为A1110U和ACV联合可能为人类皮肤HSV感染的局部治疗提供有效疗法带来了希望。
