In vitro and in vivo evaluation of thapsigargin as an antiviral agent against transmissible gastroenteritis virus.

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Yang Li, Yuanyuan Liu, Yunhang Zhang, Chen Tan, Yifei Cai, Yue Zhang, Jianing Chen, Yuguang Fu, Guangliang Liu
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引用次数: 0

Abstract

Swine enteric coronaviruses (SeCoVs) pose a significant threat to the global pig industry, but no effective drugs are available for treatment. Previous research has demonstrated that thapsigargin (TG), an ER stress inducer, has broad-spectrum antiviral effects on human coronaviruses. In this study, we investigated the impact of TG on transmissible gastroenteritis virus (TGEV) infection using cell lines, porcine intestinal organoid models, and piglets. The results showed that TG effectively inhibited TGEV replication both in vitro and ex vivo. Furthermore, animal experiments demonstrated that oral administration of TG inhibited TGEV infection in neonatal piglets and relieved TGEV-associated tissue injury. Transcriptome analyses revealed that TG improved the expression of the ER-associated protein degradation (ERAD) component and influenced the biological processes related to secretion, nutrient responses, and epithelial cell differentiation in the intestinal epithelium. Collectively, these results suggest that TG is a potential novel oral antiviral drug for the clinical treatment of TGEV infection, even for infections caused by other SeCoVs.

体外和体内评估作为抗病毒剂的硫司加精对传染性肠胃炎病毒的作用。
猪肠道冠状病毒(SeCoVs)对全球养猪业构成了严重威胁,但目前还没有有效的治疗药物。先前的研究表明,胰岛素ER应激诱导剂硫代加精(TG)对人类冠状病毒具有广谱抗病毒作用。在本研究中,我们使用细胞系、猪肠道类器官模型和仔猪研究了 TG 对传染性胃肠炎病毒(TGEV)感染的影响。结果表明,TG 能有效抑制 TGEV 在体外和体内的复制。此外,动物实验表明,口服 TG 可抑制新生仔猪的 TGEV 感染,并缓解 TGEV 相关的组织损伤。转录组分析表明,TG 改善了ER相关蛋白降解(ERAD)成分的表达,并影响了与肠上皮细胞分泌、营养反应和上皮细胞分化相关的生物过程。总之,这些结果表明 TG 是一种潜在的新型口服抗病毒药物,可用于 TGEV 感染的临床治疗,甚至可用于其他 SeCoV 引起的感染。
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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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