College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China.
Qingdao Animal Disease Prevention and Control Center, Qingdao 266100, China.
Viruses. 2023 Oct 12;15(10):2080. doi: 10.3390/v15102080.
Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that induces diarrhea and death in neonatal piglets, resulting in substantial economic losses to the global swine industry. The mechanisms of PEDV infection and the roles of host factors are still under exploration. In this study, we used the ferroptosis pathway downstream target activator (1S,3R)-RSL3 compound as a starting point, combined with the interactions of N-acetylcysteine and deferoxamine, to elucidate the effects of a series of compounds on PEDV proliferation. We also established glutathione peroxidase 4 (GPX4) gene overexpression to further elucidate the relationship between the ferroptosis pathway and PEDV. (1S,3R)-RSL3 inhibited PEDV replication in Vero cells, while N-acetylcysteine and deferoxamine promoted its proliferation. In addition, (1S,3R)-RSL3 mainly affected the replication stage of PEDV. Overexpression of GPX4 promoted PEDV proliferation, indicating that the ferroptosis pathway could influence PEDV replication in Vero cells. This study focused on the mechanism of (1S,3R)-RSL3 inhibition on PEDV, laying the foundation for exploring the pathogenic mechanisms of PEDV and drug development.
猪流行性腹泻病毒（PEDV）是一种高度传染性的冠状病毒，可引起仔猪腹泻和死亡，给全球养猪业造成巨大经济损失。PEDV 感染的机制和宿主因素的作用仍在探索中。在本研究中，我们以铁死亡途径下游靶标激活剂（1S,3R）-RSL3 化合物为起点，结合 N-乙酰半胱氨酸和去铁胺的相互作用，阐明了一系列化合物对 PEDV 增殖的影响。我们还建立了谷胱甘肽过氧化物酶 4（GPX4）基因过表达，以进一步阐明铁死亡途径与 PEDV 之间的关系。（1S,3R）-RSL3 抑制 Vero 细胞中的 PEDV 复制，而 N-乙酰半胱氨酸和去铁胺则促进其增殖。此外，（1S,3R）-RSL3 主要影响 PEDV 的复制阶段。GPX4 的过表达促进了 PEDV 的增殖，表明铁死亡途径可以影响 Vero 细胞中的 PEDV 复制。本研究重点关注（1S,3R）-RSL3 抑制 PEDV 的机制，为探索 PEDV 的致病机制和药物开发奠定了基础。
