RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis

• Published in: Viruses Vol. 15; no. 10; p. 2080
• Main Authors: Li, Yingguang, Bao, Yuwei, Li, Yan, Duan, Xiaoxiao, Dong, Shaoming, Lin, Jiaxu, Chang, Xiaoyun, Tan, Yue, Zhang, Hongliang, Shan, Hu
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2023; MDPI
• Subjects: (1S,3R)-RSL3; Acetylcysteine; Antibodies; Antiviral agents; Biotechnology; Care and treatment; Cell death; Cell proliferation; Coronavirus infections; Coronaviruses; Deferoxamine; Development and progression; Diarrhea; Drug development; Epidemics; Epidemiology; Ferroptosis; Glutathione peroxidase; GPX4; Herpes viruses; Hogs; Infections; Laboratories; Lipid peroxidation; Lipids; Medical research; Metabolism; Neonates; porcine epidemic diarrhea virus; Proteins; Replication; Transmissible gastroenteritis; Vero cells; Veterinary medicine; Viral diarrhea; Virus research; China; United States > US; Shandong China
• ISSN: 1999-4915; 1999-4915
• 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.