Sun Pei, Wang Mingge, Li Jie, Qiu Yanping, Li Hongyue, Lv Muze, Bo Zongyi, Shen Haixiao, Li Liang
College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230036, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Vet Microbiol. 2022 Sep;272:109516. doi: 10.1016/j.vetmic.2022.109516. Epub 2022 Jul 19.
Porcine epidemic diarrhea virus (PEDV) is one of the main pathogens causing severe diarrhea in piglets. Infection of the host induces apoptosis, causing huge economic losses to the pig industry. At present, the preventive and therapeutic effects of commercial vaccines are not satisfactory, and it is necessary to develop new anti-PEDV drugs. In this study, we screened the PEDV-inhibiting drug Buddlejasaponin IVb from the natural product library, and determined the inhibitory effect of Buddlejasaponin IVb on PEDV proliferation in a dose-dependent manner. By exploring the effect of Buddlejasaponin IVb on the life cycle of PEDV, it was found that Buddlejasaponin IVb mainly inhibits the replication and release stages of PEDV, but there is no report at home and abroad. In addition, Buddlejasaponin IVb can inhibit PEDV-activated NF-κB signaling pathway by downregulating PEDV or LPS induced elevation of cytokine levels (IL-6, IL-8, IL-1β, TNF-α). Finally, we returned to in vivo experiments to explore the antiviral effects of the drug in pigs. The results show that Buddlejasaponin IVb can effectively relieve the clinical symptoms and intestinal damage caused by PEDV infection in pigs. Therefore, this study will provide an important basis for the research on antiviral drugs of PEDV and its members, and at the same time provide guidance for the actual production, which has important application prospects.
猪流行性腹泻病毒（PEDV）是导致仔猪严重腹泻的主要病原体之一。宿主感染该病毒会诱导细胞凋亡，给养猪业造成巨大经济损失。目前，商业疫苗的预防和治疗效果并不理想，因此有必要开发新的抗PEDV药物。在本研究中，我们从天然产物库中筛选出了抑制PEDV的药物醉鱼草皂苷IVb，并确定了醉鱼草皂苷IVb对PEDV增殖具有剂量依赖性抑制作用。通过探究醉鱼草皂苷IVb对PEDV生命周期的影响，发现醉鱼草皂苷IVb主要抑制PEDV的复制和释放阶段，而国内外尚无相关报道。此外，醉鱼草皂苷IVb可通过下调PEDV或LPS诱导的细胞因子水平（IL-6、IL-8、IL-1β、TNF-α）升高来抑制PEDV激活的NF-κB信号通路。最后，我们回到体内实验，探究该药物在猪体内的抗病毒效果。结果表明，醉鱼草皂苷IVb可有效缓解PEDV感染猪所引起的临床症状和肠道损伤。因此，本研究将为PEDV及其相关成员的抗病毒药物研究提供重要依据，同时为实际生产提供指导，具有重要的应用前景。
