毛花洋地黄苷 C 通过调节细胞内 NRF2 的分布抑制单纯疱疹病毒 1 的复制。

Lanatoside C inhibits herpes simplex virus 1 replication by regulating NRF2 distribution within cells.

机构信息

Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, National Key Clinic of Pain Medicine, Shenzhen Nanshan People's Hospital, and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518060, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.

出版信息

Phytomedicine. 2024 Feb;124:155308. doi: 10.1016/j.phymed.2023.155308. Epub 2023 Dec 25.

DOI:10.1016/j.phymed.2023.155308

PMID:38185069

Abstract

BACKGROUND

In the past decades, extensive research has been conducted to identify new drug targets for the treatment of Herpes simplex virus type 1 (HSV-1) infections. However, the emergence of drug-resistant HSV-1 strains remains a major challenge. This necessitates the identification of new drugs with novel mechanisms of action. Lanatoside C (LanC), a cardiac glycoside (CG) approved by the US Food and Drug Administration (FDA), has demonstrated anticancer and antiviral properties. Nevertheless, its potential as an agent against HSV-1 infections and the underlying mechanism of action are currently unknown.

PURPOSE

This study aimed to investigate the antiviral activity of LanC against HSV-1 and elucidate its molecular mechanisms.

METHODS

The in vitro antiviral activity of LanC was assessed by examining the levels of viral genes, proteins, and virus titers in HSV-1-infected ARPE-19 and Vero cells. Immunofluorescence (IF) analysis was performed to determine the intracellular distribution of NRF2. Additionally, an in vivo mouse model of HSV-1 infection was developed to evaluate the antiviral activity of LanC, using indicators such as intraepidermal nerve fibers (IENFs) loss and viral gene inhibition.

RESULTS

Our findings demonstrate that LanC significantly inhibits HSV-1 replication both in vitro and in vivo. The antiviral effect of LanC is mediated by the perinuclear translocation of NRF2.

CONCLUSIONS

LanC exhibits anti-HSV-1 effects in viral infections, which are associated with the intracellular translocation of NRF2. These findings suggest that LanC has the potential to serve as a novel NRF2 modulator in the treatment of viral diseases.

摘要

背景

在过去的几十年中，已经进行了广泛的研究，以确定用于治疗单纯疱疹病毒 1 型（HSV-1）感染的新药物靶标。然而，耐药性 HSV-1 株的出现仍然是一个主要挑战。这就需要确定具有新作用机制的新药。毛地黄毒苷 C（LanC）是一种已被美国食品和药物管理局（FDA）批准的强心苷（CG），已显示出抗癌和抗病毒特性。尽管如此，其作为抗 HSV-1 感染的药物的潜力及其作用机制尚不清楚。

目的

本研究旨在研究 LanC 对 HSV-1 的抗病毒活性，并阐明其分子机制。

方法

通过检查 HSV-1 感染的 ARPE-19 和 Vero 细胞中的病毒基因、蛋白质和病毒滴度来评估 LanC 的体外抗病毒活性。免疫荧光（IF）分析用于确定 NRF2 的细胞内分布。此外，建立了 HSV-1 感染的小鼠模型，以评估 LanC 的抗病毒活性，使用表皮内神经纤维（IENFs）丧失和病毒基因抑制等指标。