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.
College of Animal Science and Technology, Jilin Agricultural Science and Technology University, Jilin, PR China.
Vet Microbiol. 2023 Jun;281:109743. doi: 10.1016/j.vetmic.2023.109743. Epub 2023 Apr 11.
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 (IC = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log TCID/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.
感染猪流行性腹泻病毒（PEDV）会导致新生仔猪出现严重的水样腹泻，给养猪业造成巨大的经济损失。在本研究中，我们通过分子对接筛选针对 3 样蛋白酶（3CLpro）的小分子药物，并进一步评估了筛选出的药物对 PEDV 的抗病毒活性。结果表明，没食子酸辛酯（OG）是一种广泛使用的食品添加剂，对 PEDV 3CLpro 的活性位点具有很强的结合亲和力。生物层干涉仪和荧光共振能量转移实验表明，OG 直接与 PEDV 3CLpro 相互作用（KD = 549 nM）并抑制 3CLpro 活性（IC = 22.15 μM）。OG 对 PEDV 在体外的复制具有很强的抑制作用。CV777 和 HM2017 株的病毒滴度分别降低了 0.58 和 0.71 log TCID/mL。在体内，感染 PEDV 的所有仔猪在感染后 48 小时（hpi）死亡，而 OG 治疗组的 75%仔猪的临床症状、病理损伤以及空肠和回肠中的病毒载量均明显缓解。此外，Western blot 结果表明，OG 对其他猪肠道冠状病毒也具有很强的抗病毒活性，包括传染性胃肠炎病毒（TGEV）、猪德尔塔冠状病毒（PDCoV）和猪急性腹泻综合征冠状病毒（SADS-CoV）。我们的研究结果表明，OG 可开发为一种新型抗 PEDV 药物。OG 可能成为一种新型广谱抗病毒药物，用于控制其他猪肠道冠状病毒。
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