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丹酚酸 A 通过直接使病毒粒子失活来抑制伪狂犬病毒感染。

Salvianolic acid A inhibits pseudorabies virus infection by directly inactivating the virus particle.

机构信息

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, PR China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Henan, Agricultural University, Zhengzhou 450046, PR China.

出版信息

Phytomedicine. 2024 Nov;134:156015. doi: 10.1016/j.phymed.2024.156015. Epub 2024 Sep 1.

DOI:10.1016/j.phymed.2024.156015
PMID:39244942
Abstract

BACKGROUND

Pseudorabies virus (PRV), a member of the family Herpesviridae, is responsible for significant economic losses in the pig industry and has recently been associated with human viral encephalitis, leading to severe neurological symptoms post-recovery. Despite the widespread impact of PRV, there are currently no approved effective drugs for treating PRV-related diseases in humans or pigs. Therefore, the exploration and discovery of safe and effective drugs for the prevention and treatment of PRV infection is of paramount importance.

PURPOSE

The objective of this study is to screen and identify natural compounds with antiviral activity against PRV.

METHODS

First, we used a strain of PRV with green fluorescent protein (PRV-GFP) to screen a natural product chemical library to identify potential antiviral drugs. Next, we assessed the antiviral abilities of salvianolic acid A (SAA) in vitro using virus titer assay, qPCR, and IFA. We investigated the mechanisms of SAA's antiviral activity through viral attachment, internalization, inactivation, and nuclease digestion assay. Finally, we evaluated the efficacy of SAA in inactivating PRV using mice as the experimental subjects.

RESULTS

This study screened 206 natural compounds for anti-PRV activity in vitro, resulting in the identification of seven potential antiviral agents. Notably, SAA emerged as a promising candidate with significant anti-PRV activity. The mechanism of action may be that SAA can directly inactivate the virus by disrupting viral envelope. In vivo experiments have shown that pre-incubation of SAA and PRV can effectively inhibit the infectivity and pathogenicity of PRV in mice.

CONCLUSION

This study offers valuable insights into the antiviral properties of SAA, potentially informing strategies for controlling PRV epidemics and treating related diseases in both humans and animals.

摘要

背景

猪伪狂犬病病毒(PRV)是疱疹病毒科的一员,它给养猪业造成了巨大的经济损失,最近还与人类病毒性脑炎有关,导致患者康复后出现严重的神经症状。尽管 PRV 的影响广泛,但目前尚无批准用于治疗人类或猪 PRV 相关疾病的有效药物。因此,探索和发现预防和治疗 PRV 感染的安全有效的药物至关重要。

目的

本研究旨在筛选和鉴定具有抗 PRV 活性的天然化合物。

方法

首先,我们使用带有绿色荧光蛋白(PRV-GFP)的 PRV 株筛选天然产物化学库,以鉴定潜在的抗病毒药物。接下来,我们使用病毒滴度测定、qPCR 和 IFA 评估了丹参酸 A(SAA)在体外的抗病毒能力。我们通过病毒附着、内化、失活和核酸酶消化测定研究了 SAA 的抗病毒活性机制。最后,我们评估了 SAA 对小鼠 PRV 的灭活效果。

结果

本研究在体外筛选了 206 种天然化合物以寻找抗 PRV 活性,鉴定出了七种有潜力的抗病毒药物。值得注意的是,SAA 是一种很有前途的候选药物,具有显著的抗 PRV 活性。其作用机制可能是通过破坏病毒包膜直接使病毒失活。体内实验表明,SAA 与 PRV 预孵育可有效抑制 PRV 在小鼠体内的感染性和致病性。

结论

本研究为 SAA 的抗病毒特性提供了有价值的见解,可能为控制 PRV 流行和治疗人类和动物相关疾病提供策略。

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