Department of Ophthalmology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Ophthalmology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, 22# Hankou Road, Nanjing, Jiangsu, 210093, China.
Virol J. 2024 May 27;21(1):118. doi: 10.1186/s12985-024-02384-0.
Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.
单纯疱疹病毒 1 型（HSV-1）感染眼睛会导致单纯疱疹性角膜炎（HSK），这导致患者视力丧失甚至失明。然而，HSV 的耐药率正在上升；因此，必须开发具有足够安全性的新型抗病毒药物。目前，我们评估了 502 种天然化合物的抗 HSV-1 活性及其降低 HSV-1 诱导的细胞病变效应的能力。我们选择 harmol 进行进一步研究，因为它表现出最高的抗病毒活性。我们发现 harmol 抑制 HSV-1 F 和 HSV-1/153（一种临床耐药株）的复制，EC 值分别为 9.34 µM 和 5.84 µM。此外，harmol 减少了角膜组织中的 HSV-1 复制和泪液中的病毒子代产生，还减轻了与 HSK 相关的早期角膜表面病变。例如，harmol 治疗在 HSK 小鼠中保存了角膜厚度和神经密度。有趣的是，harmol 对 HSV-1/153 诱导的 HSK 在小鼠模型中也显示出有希望的抗病毒作用。此外，harmol 与阿昔洛韦（ACV）联合治疗在体外的抗病毒效果优于单独使用任何一种药物。因此，harmol 可能是治疗 HSK 的一种有前途的治疗药物。
