The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Vision Institute, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Molecules. 2023 Jun 29;28(13):5078. doi: 10.3390/molecules28135078.
Adenoviruses are the major cause of ocular viral infections worldwide. Currently, there is no approved antiviral treatment for these eye infections. Cyclopentenylcytosine (CPE-C) is an antiviral that has demonstrated activity against more than 20 viruses. The goals of the current study were to determine the in vitro and in vivo antiviral activity of CPE-C as well as its ocular toxicity. Antiviral activity was evaluated in vitro using standard plaque reduction assays to determine the 50% effective concentrations (ECs) and in vivo in the Ad5/NZW rabbit ocular replication model. Ocular toxicity was determined in uninfected rabbit eyes following topical ocular application. The in vitro EC50s for CPE-C ranged from 0.03 to 0.059 μg/mL for nine adenovirus types that commonly infect the eye. Ocular toxicity testing determined CPE-C to be non-irritating or practically non-irritating by Draize scoring. In vivo, 3% CPE-C topically administered 4X or 2X daily for 7 days to adenovirus-infected eyes demonstrated effective antiviral activity compared with the negative control and comparable antiviral activity to the positive control, 0.5% cidofovir, topically administered twice daily for 7 days. We conclude CPE-C was relatively non-toxic to rabbit eyes and demonstrated potent anti-adenoviral activity in vitro and in vivo.
腺病毒是全球眼部病毒感染的主要原因。目前，针对这些眼部感染，尚无批准的抗病毒治疗方法。环戊烯胞苷（CPE-C）是一种具有抗多种 20 余种病毒活性的抗病毒药物。本研究的目的是确定 CPE-C 的体外和体内抗病毒活性及其眼部毒性。使用标准蚀斑减少测定法在体外评估抗病毒活性，以确定 50%有效浓度（EC），并在 Ad5/NZW 兔眼部复制模型中进行体内评估。在未感染的兔眼进行局部眼应用后，确定眼部毒性。九种常见眼部感染的腺病毒类型的 CPE-C 的体外 EC50 范围为 0.03 至 0.059μg/mL。眼部毒性测试表明 CPE-C 通过 Draize 评分是非刺激性或几乎无刺激性的。在体内，用 3% CPE-C 局部每日给药 4 次或 2 次，连续 7 天，用于感染腺病毒的眼睛，与阴性对照相比，具有有效的抗病毒活性，与阳性对照（0.5%西多福韦）相比，每日两次给药，连续 7 天。我们得出结论，CPE-C 对兔眼相对无毒，并且在体外和体内均显示出强大的抗腺病毒活性。
