2. Academic Validation
  3. Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV

Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV

  • Vet Microbiol. 2023 Apr 11;281:109743. doi: 10.1016/j.vetmic.2023.109743.
Mingjun Su 1,  Baishuang Yin 2,  Xiaoxu Xing 3,  Zijian Li 3,  Jiyu Zhang 4,  Shufeng Feng 4,  Lu Li 3,  Feiyu Zhao 3,  Xu Yang 3,  Shiping Yu 3,  Jun Wang 3,  Yongchen Zhang 3,  Da Shi 4,  Jianfei Chen 4,  Li Feng 4,  Donghua Guo 3,  Dongbo Sun 5
Affiliations

Affiliations

  • 1 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, PR China; College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang A&F University, 666 Wusu Street, Lin'an District, Hangzhou, Zhejiang Province 311300, PR China.
  • 2 College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin, PR China.
  • 3 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, PR China.
  • 4 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
  • 5 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, PR China. Electronic address: dongbosun@126.com.
PMID: 37062110 DOI: 10.1016/j.vetmic.2023.109743
Abstract

Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like Protease (3CLpro) by molecular docking, and further evaluated the Antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong Antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel Antiviral drug against PEDV. The OG exhibited a potential broad-spectrum Antiviral drug for control of other swine enteric coronaviruses.

Keywords

3C-like protease; Broad-spectrum antiviral drug; Octyl gallate; Porcine epidemic diarrhea virus; Swine enteric coronaviruses.

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