In vitro antiviral activity of the RdRp inhibitor 4’-fluorouridine against a porcine teschovirus clinical isolate

IF 2.5 4区医学 Q3 VIROLOGY

Archives of Virology Pub Date : 2026-10-20 DOI:10.1007/s00705-026-06750-x

Wenhui Zhang, Luhua Zhang, Xiaobo He, Fei Wang, Zhentao Zhang, Guohua Chen, Weike Li

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Abstract

Porcine Teschovirus (PTV) is an economically significant swine pathogen with a global distribution that can cause severe neurological, respiratory, and reproductive diseases. However, no specific vaccines or antiviral drugs are currently available. To address the absence of specific antiviral therapies for PTV, this study aimed to identify a clinically promising antiviral candidate through in vitro compound screening. We began by isolating and purified a contemporary PTV strain (PTV/Shandong/2024) from a clinical swab of a dead piglet. We also established a strain-specific RT-qPCR assay to accurately quantify PTV RNA load. A subsequent targeted screen of a hepatitis C virus (HCV) inhibitor library identified the nucleoside analog 4’-fluorouridine (4’-FLU) as a potent inhibitor of PTV replication in vitro. Treatment with 4’-FLU significantly reduced viral load and cytopathic effects in infected PK-15 cells. The compound exhibited potent antiviral activity, with a half maximal inhibitory concentration (IC₅₀) of 1.234 µM, and low cytotoxicity, with a half maximal cytotoxic concentration (CC₅₀) of 295.7 µM. This resulted in a high selectivity index of 239.6, indicating a wide therapeutic window. Time-of-addition experiments revealed that 4’-FLU acts primarily during the early stages of viral replication. These results provide the first evidence that 4’-FLU suppresses PTV replication in vitro supporting its further evaluation as a candidate antiviral against PTV.

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RdRp抑制剂4′-氟吡啶对猪teschovirus临床分离物的体外抗病毒活性研究。

猪Teschovirus （PTV）是一种经济上重要的猪病原体，具有全球分布，可引起严重的神经、呼吸和生殖疾病。然而，目前还没有特定的疫苗或抗病毒药物可用。为了解决PTV缺乏特异性抗病毒治疗的问题，本研究旨在通过体外化合物筛选确定具有临床前景的抗病毒候选药物。我们首先从一只死仔猪的临床拭子中分离并纯化了一株当代PTV菌株（PTV/Shandong/2024）。我们还建立了一种菌株特异性RT-qPCR方法来准确定量PTV RNA载量。随后对丙型肝炎病毒（HCV）抑制剂文库的靶向筛选发现核苷类似物4'-氟吡啶（4'-FLU）是PTV体外复制的有效抑制剂。4′-FLU治疗显著降低了感染PK-15细胞的病毒载量和细胞病变效应。该化合物具有强大的抗病毒活性，最大抑制浓度（IC₅₀）的一半为1.234µM，细胞毒性低，最大细胞毒性浓度（CC₅₀）的一半为295.7µM。这导致了239.6的高选择性指数，表明一个宽的治疗窗口。添加时间实验显示，4'-FLU主要在病毒复制的早期阶段起作用。这些结果提供了4'-FLU在体外抑制PTV复制的第一个证据，支持其作为PTV候选抗病毒药物的进一步评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives of Virology 医学-病毒学

CiteScore

5.10

自引率

7.40%

发文量

324

审稿时长

4.5 months

期刊介绍： Archives of Virology publishes original contributions from all branches of research on viruses, virus-like agents, and virus infections of humans, animals, plants, insects, and bacteria. Coverage spans a broad spectrum of topics, from descriptions of newly discovered viruses, to studies of virus structure, composition, and genetics, to studies of virus interactions with host cells, organisms and populations. Studies employ molecular biologic, molecular genetics, and current immunologic and epidemiologic approaches. Contents include studies on the molecular pathogenesis, pathophysiology, and genetics of virus infections in individual hosts, and studies on the molecular epidemiology of virus infections in populations. Also included are studies involving applied research such as diagnostic technology development, monoclonal antibody panel development, vaccine development, and antiviral drug development.Archives of Virology wishes to publish obituaries of recently deceased well-known virologists and leading figures in virology.