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

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

  • Vet Res. 2024 Aug 2;55(1):97. doi: 10.1186/s13567-024-01359-x.
Yang Li 1,  Yuanyuan Liu 1 2 3,  Yunhang Zhang 1 4,  Chen Tan 1 4,  Yifei Cai 1 5,  Yue Zhang 1,  Jianing Chen 1,  Yuguang Fu 1,  Guangliang Liu 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science, Lanzhou, China.
  • 2 Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China.
  • 3 College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
  • 4 Molecular and Cellular Epigenetics (GIGA), University of Liege, Liege, Belgium.
  • 5 Human Nutrition and Health Group, VLAG, Wageningen University and Research, Wageningen, The Netherlands.
  • 6 State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science, Lanzhou, China. LiuGuangliang01@caas.cn.
  • 7 Hainan Key Laboratory of Tropical Animal Breeding and Infectious Disease Research, Institute of Animal Husbandry and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, China. LiuGuangliang01@caas.cn.
PMID: 39095890 DOI: 10.1186/s13567-024-01359-x
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.

Keywords

ERS; TGEV; antiviral drug; intestinal organoids; thapsigargin.

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