RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis

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 st...

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Main Authors: Yingguang Li, Yuwei Bao, Yan Li, Xiaoxiao Duan, Shaoming Dong, Jiaxu Lin, Xiaoyun Chang, Yue Tan, Hongliang Zhang, Hu Shan
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/10/2080
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author Yingguang Li
Yuwei Bao
Yan Li
Xiaoxiao Duan
Shaoming Dong
Jiaxu Lin
Xiaoyun Chang
Yue Tan
Hongliang Zhang
Hu Shan
author_facet Yingguang Li
Yuwei Bao
Yan Li
Xiaoxiao Duan
Shaoming Dong
Jiaxu Lin
Xiaoyun Chang
Yue Tan
Hongliang Zhang
Hu Shan
author_sort Yingguang Li
collection DOAJ
description 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.
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spelling doaj.art-c36f08a938ae4994896d4c42006e85b62023-11-19T18:27:59ZengMDPI AGViruses1999-49152023-10-011510208010.3390/v15102080RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating FerroptosisYingguang Li0Yuwei Bao1Yan Li2Xiaoxiao Duan3Shaoming Dong4Jiaxu Lin5Xiaoyun Chang6Yue Tan7Hongliang Zhang8Hu Shan9College of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaQingdao Animal Disease Prevention and Control Center, Qingdao 266100, ChinaQingdao Animal Disease Prevention and Control Center, Qingdao 266100, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaCollege of Veterinary Medicine, Shandong Collaborative Innovation Center for Development of Veterinary Pharmaceuticals, Qingdao Agricultural University, Qingdao 266109, ChinaPorcine 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.https://www.mdpi.com/1999-4915/15/10/2080(1S,3R)-RSL3GPX4porcine epidemic diarrhea virusferroptosis
spellingShingle Yingguang Li
Yuwei Bao
Yan Li
Xiaoxiao Duan
Shaoming Dong
Jiaxu Lin
Xiaoyun Chang
Yue Tan
Hongliang Zhang
Hu Shan
RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
Viruses
(1S,3R)-RSL3
GPX4
porcine epidemic diarrhea virus
ferroptosis
title RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
title_full RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
title_fullStr RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
title_full_unstemmed RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
title_short RSL3 Inhibits Porcine Epidemic Diarrhea Virus Replication by Activating Ferroptosis
title_sort rsl3 inhibits porcine epidemic diarrhea virus replication by activating ferroptosis
topic (1S,3R)-RSL3
GPX4
porcine epidemic diarrhea virus
ferroptosis
url https://www.mdpi.com/1999-4915/15/10/2080
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