丹酚酸A通过阻断糖蛋白b介导的吸附和膜融合作为单纯疱疹病毒的双重抑制剂

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-25 DOI:10.1016/j.phymed.2025.156910

Han Yan , Haihua Li , Xiayu Chen , Jie Wang , Jiayi Yang , Zhongqiu Xu , Cui Hao , Wei Wang

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引用次数: 0

摘要

背景研制高效、低毒的新型抗单纯疱疹病毒（HSV）药物具有重要意义。丹参酚酸A （SAA）是一种来自丹参根的二苯甲酸三聚体，显示出对肠道病毒71型（EV71）、伪狂犬病毒（PRV）和SARS-CoV-2的广谱抗病毒活性。但目前尚无关于其抗hsv活性的研究报道。目的通过体外和体内两种方法研究SAA抗hsv的作用，并阐明其作用机制。方法采用细胞病变效应（CPE）抑制法、western blot法和病毒斑块法检测SAA体外抗hsv的作用。通过杀病毒实验、药物亲和力反应靶稳定性（DARTS）实验、细胞热移实验（CETSA）和肝素结合实验研究SAA抗hsv的作用机制。采用小鼠鼻内HSV-1脑炎模型和阴道HSV-2感染模型评价SAA的体内抗hsv效果。结果saa抑制HSV-1和HSV-2在不同细胞中的增殖，且毒性较低，优于阿昔洛韦。SAA通过破坏病毒粒子膜直接灭活HSV。SAA与病毒表面糖蛋白B （gB）相互作用，阻断HSV吸附和进入。SAA治疗可显著提高小鼠存活率，减轻HSV-1和HSV-2感染小鼠的炎症症状，并降低病毒滴度。结论saa通过与gB相互作用，阻断HSV进入，使HSV颗粒破裂失活，具有明显的体内外抗HSV作用。这些发现支持其作为疱疹性脑炎和生殖器疱疹的新型治疗剂的潜力。

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Salvianolic acid A acts as a herpes simplex virus dual inhibitor by blocking glycoprotein B-mediated adsorption and membrane fusion

Background

The development of novel anti-herpes simplex virus (HSV) agents with high efficacy and low toxicity is great importance. Salvianolic acid A (SAA), a stilbenoid caffeic acid trimer from Salvia miltiorrhiza Bunge roots, has shown broad-spectrum antiviral activities against enterovirus 71 (EV71), pseudorabies virus (PRV), and SARS-CoV-2. However, no studies on its anti-HSV activity have been reported yet.

Purpose

To investigate the anti-HSV effects of SAA through both in vitro and in vivo approaches and to elucidate its mechanisms of action.

Methods

The anti-HSV effects of SAA in vitro were determined by cytopathic effect (CPE) inhibition assay, western blot assay and viral plaque assay. The virucidal assay, drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA) and heparin binding assay investigated SAA’s anti-HSV mechanism. The in vivo anti-HSV efficacy of SAA was evaluated using murine model for intranasal HSV-1 encephalitis and vaginal HSV-2 infection model.

Results

SAA suppressed HSV-1 and HSV-2 multiplication in different cells with low toxicity, superior to acyclovir. SAA directly inactivates HSV by disrupting virion membrane. SAA interacts with viral surface glycoprotein B (gB) to block HSV adsorption and entry. SAA treatment significantly improved mice survival, attenuated inflammatory symptoms, and reduced viral titers in HSV-1 and HSV-2 infected mice.

Conclusion

SAA possesses significant anti-HSV effects in vitro and in vivo through interaction with gB to block HSV entry and cause HSV particle rupture and inactivation. These findings support its potential as a novel therapeutic agent for herpetic encephalitis and genital herpes.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.