RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
Yingguang Li,
Yuwei Bao,
Yan Li,
Xiaoxiao Duan,
Shaoming Dong,
Jiaxu Lin,
Xiaoyun Chang,
Yue Tan,
Hongliang Zhang,
Hu Shan
Affiliations
Yingguang Li
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Yuwei Bao
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Yan Li
Qingdao Animal Disease Prevention and Control Center, Qingdao 266100, China
Xiaoxiao Duan
Qingdao Animal Disease Prevention and Control Center, Qingdao 266100, China
Shaoming Dong
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Jiaxu Lin
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Xiaoyun Chang
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Yue Tan
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Hongliang Zhang
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
Hu Shan
College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, China
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.
