Jiang Limin, Gu Minghui, Xiao Jiawei, Zhao Yingying, Shen Fanbo, Guo Xingyang, Li Hansong, Guo Donghua, Li Chunqiu, Zhu Qinghe, Yang Dan, Xing Xiaoxu, Sun Dongbo
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, China.
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Sartu District, Daqing 163319, China.
Virology. 2025 Mar;604:110406. doi: 10.1016/j.virol.2025.110406. Epub 2025 Jan 16.
Porcine epidemic diarrhea virus (PEDV) can cause severe diarrhea death in newborn piglets, resulting in significant economic losses for the pig industry. Therefore, the advancement of safe and effective anti-PEDV drugs for the treatment of PEDV is of paramount importance. In this study, molecular docking was used to screen natural drugs that can target PEDV 3C like protease (3CLpro). As well, the anti-PEDV effects of the screened drugs were evaluated in vitro and in vivo. Molecular docking and molecular dynamics (MD) simulation results showed that ethyl caffeate (EC) could efficiently bind to the active cavity of PEDV 3CLpro. Biolayer interferometry (BLI) and fluorescence resonance energy transfer (FRET) analyses demonstrated that EC directly interacts with PEDV 3CLpro (K = 1650 μM) and inhibits the activity of 3CLpro (IC = 33.87 μM). EC has been shown to significantly inhibit the replication of PEDV in Vero E6 cells. The half maximal inhibitory concentration (CC) and half-effective concentration (EC) were determined to be 283.1 μM and 8.641 μM, respectively, yielding a selectivity index as high as 32.7. Furthermore, EC was evaluated using a piglet infection model for PEDV. It demonstrated the ability to inhibit PEDV infection in vivo and improve the survival rate of piglets (3/5, 60%). Compared to the control group, oral administration of EC significantly reduced intestinal pathological damage and viral load. Our study indicated that EC, targeting PEDV 3CLpro, is a safe and effective anti-PEDV drug with promising clinical application prospects.
猪流行性腹泻病毒（PEDV）可导致新生仔猪严重腹泻死亡，给养猪业造成重大经济损失。因此，研发安全有效的抗PEDV药物用于治疗PEDV至关重要。在本研究中，采用分子对接技术筛选可靶向PEDV 3C样蛋白酶（3CLpro）的天然药物。此外，还在体外和体内评估了筛选出的药物的抗PEDV效果。分子对接和分子动力学（MD）模拟结果表明，咖啡酸乙酯（EC）可有效结合到PEDV 3CLpro的活性腔中。生物层干涉术（BLI）和荧光共振能量转移（FRET）分析表明，EC直接与PEDV 3CLpro相互作用（K = 1650 μM）并抑制3CLpro的活性（IC = 33.87 μM）。已证明EC可显著抑制PEDV在Vero E6细胞中的复制。测定其半数细胞毒性浓度（CC）和半数有效浓度（EC）分别为283.1 μM和8.641 μM，选择性指数高达32.7。此外，使用PEDV仔猪感染模型对EC进行了评估。结果表明，EC能够在体内抑制PEDV感染并提高仔猪的存活率（3/5，60%）。与对照组相比，口服EC可显著减轻肠道病理损伤并降低病毒载量。我们的研究表明，靶向PEDV 3CLpro的EC是一种安全有效的抗PEDV药物，具有良好的临床应用前景。
