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

文献类型: 外文期刊

作者: Li, Yang 1 ; Liu, Yuanyuan 1 ; Zhang, Yunhang 1 ; Tan, Chen 1 ; Cai, Yifei 1 ; Zhang, Yue 1 ; Chen, Jianing 1 ; Fu, Yuguang 1 ; Liu, Guangliang 1 ;

作者机构: 1.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Lanzhou, Peoples R China

2.Hainan Acad Agr Sci, Inst Anim Husb & Vet Med, Hainan Key Lab Trop Anim Breeding & Infect Dis Res, Haikou, Peoples R China

3.Xinjiang Agr Univ, Coll Vet Med, Urumqi, Peoples R China

4.Univ Liege, Mol & Cellular Epigenet GIGA, Liege, Belgium

5.Wageningen Univ & Res, Human Nutr & Hlth Grp, VLAG, Wageningen, Netherlands

关键词: thapsigargin; intestinal organoids; ERS; antiviral drug; TGEV

期刊名称:VETERINARY RESEARCH ( 影响因子:3.7; 五年影响因子:3.8 )

ISSN: 0928-4249

年卷期: 2024 年 55 卷 1 期

页码:

收录情况: SCI

摘要: 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.

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