Levistolide A Inhibits PEDV Replication via Inducing ROS Generation

Porcine epidemic diarrhea virus (PEDV) variant strains adversely affect the production of pigs globally. Vaccines derived from PEDV traditional strains impart less protection against the variant strains. Moreover, sequence diversity among different PEDV variant strains is also complicated. This nece...

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Main Authors: Wei Zeng, Jingping Ren, Zhonghua Li, Changsheng Jiang, Qi Sun, Chang Li, Wan Li, Wentao Li, Qigai He
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/2/258
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author Wei Zeng
Jingping Ren
Zhonghua Li
Changsheng Jiang
Qi Sun
Chang Li
Wan Li
Wentao Li
Qigai He
author_facet Wei Zeng
Jingping Ren
Zhonghua Li
Changsheng Jiang
Qi Sun
Chang Li
Wan Li
Wentao Li
Qigai He
author_sort Wei Zeng
collection DOAJ
description Porcine epidemic diarrhea virus (PEDV) variant strains adversely affect the production of pigs globally. Vaccines derived from PEDV traditional strains impart less protection against the variant strains. Moreover, sequence diversity among different PEDV variant strains is also complicated. This necessitates developing alternative antiviral strategies for defending against PEDV. This study explored a natural product, Levistolide A (LA), to possess antiviral activity against PEDV. LA was found to suppress PEDV replication in a dose-dependent manner. And the inhibitory effect of LA against PEDV was maintained in the course of time. In terms of viral RNA and protein production, LA also showed a strong inhibitory effect. In addition, LA was indicated to inhibit PEDV from attaching to the cellular membrane or penetrating the cells. Further study revealed that LA can induce the generation of reactive oxygen species (ROS), and the corresponding inhibitor, NAC, was found to antagonize the effect of LA on inhibiting PEDV replication. This illustrated that the LA-induced ROS generation played an important role in its anti-PEDV activity. LA was also identified to stimulate ER stress, which is an important consequence of ROS production and was proven to be able to inhibit PEDV replication. To conclude, this study revealed that LA can inhibit PEDV replication via inducing ROS generation.
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spelling doaj.art-677cbda593e046df85c1b5df261ecf782023-11-23T22:30:01ZengMDPI AGViruses1999-49152022-01-0114225810.3390/v14020258Levistolide A Inhibits PEDV Replication via Inducing ROS GenerationWei Zeng0Jingping Ren1Zhonghua Li2Changsheng Jiang3Qi Sun4Chang Li5Wan Li6Wentao Li7Qigai He8State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaHubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan 430023, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaState Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaPorcine epidemic diarrhea virus (PEDV) variant strains adversely affect the production of pigs globally. Vaccines derived from PEDV traditional strains impart less protection against the variant strains. Moreover, sequence diversity among different PEDV variant strains is also complicated. This necessitates developing alternative antiviral strategies for defending against PEDV. This study explored a natural product, Levistolide A (LA), to possess antiviral activity against PEDV. LA was found to suppress PEDV replication in a dose-dependent manner. And the inhibitory effect of LA against PEDV was maintained in the course of time. In terms of viral RNA and protein production, LA also showed a strong inhibitory effect. In addition, LA was indicated to inhibit PEDV from attaching to the cellular membrane or penetrating the cells. Further study revealed that LA can induce the generation of reactive oxygen species (ROS), and the corresponding inhibitor, NAC, was found to antagonize the effect of LA on inhibiting PEDV replication. This illustrated that the LA-induced ROS generation played an important role in its anti-PEDV activity. LA was also identified to stimulate ER stress, which is an important consequence of ROS production and was proven to be able to inhibit PEDV replication. To conclude, this study revealed that LA can inhibit PEDV replication via inducing ROS generation.https://www.mdpi.com/1999-4915/14/2/258porcine epidemic diarrhea virusLevistolide Areactive oxygen speciesantiviral
spellingShingle Wei Zeng
Jingping Ren
Zhonghua Li
Changsheng Jiang
Qi Sun
Chang Li
Wan Li
Wentao Li
Qigai He
Levistolide A Inhibits PEDV Replication via Inducing ROS Generation
Viruses
porcine epidemic diarrhea virus
Levistolide A
reactive oxygen species
antiviral
title Levistolide A Inhibits PEDV Replication via Inducing ROS Generation
title_full Levistolide A Inhibits PEDV Replication via Inducing ROS Generation
title_fullStr Levistolide A Inhibits PEDV Replication via Inducing ROS Generation
title_full_unstemmed Levistolide A Inhibits PEDV Replication via Inducing ROS Generation
title_short Levistolide A Inhibits PEDV Replication via Inducing ROS Generation
title_sort levistolide a inhibits pedv replication via inducing ros generation
topic porcine epidemic diarrhea virus
Levistolide A
reactive oxygen species
antiviral
url https://www.mdpi.com/1999-4915/14/2/258
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