Quercetin inhibits herpes simplex virus 1 replication in corneal epithelium and suppresses keratitis progression

Yubin Yu; Sihao Liu; Qinghua Liu; Xiuping Liu; Kaili Wu

doi:10.1016/j.virs.2025.07.007

August 2025

. doi: 10.1016/j.virs.2025.07.007

Citation: Yubin Yu, Sihao Liu, Qinghua Liu, Xiuping Liu, Kaili Wu. Quercetin inhibits herpes simplex virus 1 replication in corneal epithelium and suppresses keratitis progression .VIROLOGICA SINICA, 2025, 40(4) : 647-657. http://dx.doi.org/10.1016/j.virs.2025.07.007

槲皮素抑制1型单纯疱疹病毒在角膜上皮中的复制并抑制角膜炎的进展

俞余彬 ^a,b ,
刘思豪 ^a ,
刘清华 ^a ,
刘秀平 ^a ,
吴开力 ^a,,

a 中山大学中山眼科中心, 国家眼科学重点实验室, 广东省眼部疾病临床医学研究中心;
b 温州医科大学附属第二医院、育英儿童医院眼科Science, Guangzhou, 510060, China

通讯作者： 吴开力, wukaili@mail.sysu.edu.cn
收稿日期： 2024-10-12
录用日期： 2025-07-11

摘要

槲皮素是一种具有强大抗病毒活性的天然化合物，然而其在治疗单纯疱疹性角膜炎（HSK）中的作用仍有待探索。本研究旨在探究槲皮素对1型单纯疱疹病毒（HSV-1）的抗病毒效应。在人角膜上皮细胞（HCECs）中模拟HSV-1感染的不同阶段，作者发现30 μmol/L的槲皮素主要通过阻断病毒吸附阶段来抑制病毒复制。RNA测序及后续分析显示，槲皮素能以剂量依赖的方式上调核因子E2相关因子2（Nrf2）的表达。敲低Nrf2的表达则会部分削弱槲皮素的抗病毒作用。在小鼠模型中，局部应用100 μmol/L的槲皮素能够有效减轻HSK的严重程度、降低泪液中的病毒滴度，并抑制病毒蛋白VP16在角膜及三叉神经节中的表达。这些发现证实了槲皮素对HSV-1的抗病毒作用，为后续阐明其治疗HSK的作用机制提供了重要基础。
- 槲皮素
- , 1型单纯疱疹病毒 (HSV-1)
- , 单纯疱疹病毒性角膜炎 (HSK)
- , Nrf2
- , 抗病毒

Quercetin inhibits herpes simplex virus 1 replication in corneal epithelium and suppresses keratitis progression

Yubin Yu ^a,b ,
Sihao Liu ^a ,
Qinghua Liu ^a ,
Xiuping Liu ^a ,
Kaili Wu ^a,,

a. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China;
b. Department of Ophthalmology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325035, China

Corresponding author: Kaili Wu, wukaili@mail.sysu.edu.cn
Received Date: 12 October 2024
Accepted Date: 11 July 2025

Abstract

Quercetin is a natural compound with potent antiviral effects; however, its role in the treatment of herpes simplex keratitis (HSK) remains underexplored. Here, we investigated the antiviral effects of quercetin against herpes simplex virus 1 (HSV-1). By examining different phases of viral infection in human corneal epithelial cells (HCECs), we found that 30 μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment. RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2 (Nrf2) was upregulated by quercetin in a dose-dependent manner. Knocking down Nrf2 partially compromised quercetin's antiviral effect. Importantly, topical application of 100 μmol/L quercetin alleviated HSK severity in mice, reduced viral titers in tears, and inhibited VP16 expression in the cornea and trigeminal ganglia. These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.
- Quercetin
- , Herpes simplex virus type 1 (HSV-1)
- , Herpes simplex keratitis (HSK)
- , Nrf2
- , Antiviral

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