Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities

African swine fever (ASF) is a highly contagious and severe infectious disease caused by African swine fever virus (ASFV). The disease significantly threatens the sustainable development of the global pig industry. Unfortunately, to date, no safe and efficacious vaccines are commercially available e...

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Main Authors: Di Liu, Lian-Feng Li, Huanjie Zhai, Tao Wang, Jing Lan, Mengxiang Cao, Meng Yao, Yijing Wang, Jia Li, Xin Song, Yuan Sun, Hua-Ji Qiu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2469662
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author Di Liu
Lian-Feng Li
Huanjie Zhai
Tao Wang
Jing Lan
Mengxiang Cao
Meng Yao
Yijing Wang
Jia Li
Xin Song
Yuan Sun
Hua-Ji Qiu
author_facet Di Liu
Lian-Feng Li
Huanjie Zhai
Tao Wang
Jing Lan
Mengxiang Cao
Meng Yao
Yijing Wang
Jia Li
Xin Song
Yuan Sun
Hua-Ji Qiu
author_sort Di Liu
collection DOAJ
description African swine fever (ASF) is a highly contagious and severe infectious disease caused by African swine fever virus (ASFV). The disease significantly threatens the sustainable development of the global pig industry. Unfortunately, to date, no safe and efficacious vaccines are commercially available except in Vietnam. Antioxidative stress is a critical factor in antiviral strategies. In this study, we show that ASFV infection elevates the level of reactive oxygen species (ROS) and suppresses the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in vitro and in vivo. Moreover, overexpressing Nrf2 can significantly inhibit ASFV replication. Through high-throughput screening of natural small molecules against ASFV, we identify resveratrol (RES), an Nrf2 activator, as a compound capable of inducing the cellular antiviral responses and effectively inhibiting ASFV replication in primary porcine alveolar macrophages (PAMs). Notably, untargeted metabolomics profiling reveals that glutathione emerges as a primary differential metabolite related to the antiviral activities of RES against ASFV. Mechanistically, RES exerts its antiviral effects and attenuates the elevated level of ROS caused by ASFV infection by inducing the production of reduced glutathione (GSH) via the activation of the Nrf2 signaling pathway. In conclusion, RES exhibits broad efficacy as a potentially effective compound for inhibiting ASFV infection and alleviating the oxidative stress induced by ASFV infection via the Nrf2 signaling pathway.
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spelling doaj-art-efab13a372db45ac91be9a44c20aa98a2025-08-20T01:56:42ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2469662Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activitiesDi Liu0Lian-Feng Li1Huanjie Zhai2Tao Wang3Jing Lan4Mengxiang Cao5Meng Yao6Yijing Wang7Jia Li8Xin Song9Yuan Sun10Hua-Ji Qiu11State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaState Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People’s Republic of ChinaAfrican swine fever (ASF) is a highly contagious and severe infectious disease caused by African swine fever virus (ASFV). The disease significantly threatens the sustainable development of the global pig industry. Unfortunately, to date, no safe and efficacious vaccines are commercially available except in Vietnam. Antioxidative stress is a critical factor in antiviral strategies. In this study, we show that ASFV infection elevates the level of reactive oxygen species (ROS) and suppresses the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in vitro and in vivo. Moreover, overexpressing Nrf2 can significantly inhibit ASFV replication. Through high-throughput screening of natural small molecules against ASFV, we identify resveratrol (RES), an Nrf2 activator, as a compound capable of inducing the cellular antiviral responses and effectively inhibiting ASFV replication in primary porcine alveolar macrophages (PAMs). Notably, untargeted metabolomics profiling reveals that glutathione emerges as a primary differential metabolite related to the antiviral activities of RES against ASFV. Mechanistically, RES exerts its antiviral effects and attenuates the elevated level of ROS caused by ASFV infection by inducing the production of reduced glutathione (GSH) via the activation of the Nrf2 signaling pathway. In conclusion, RES exhibits broad efficacy as a potentially effective compound for inhibiting ASFV infection and alleviating the oxidative stress induced by ASFV infection via the Nrf2 signaling pathway.https://www.tandfonline.com/doi/10.1080/22221751.2025.2469662African swine fever virusoxidative stressNrf2 signaling pathwayresveratrolantiviral activity
spellingShingle Di Liu
Lian-Feng Li
Huanjie Zhai
Tao Wang
Jing Lan
Mengxiang Cao
Meng Yao
Yijing Wang
Jia Li
Xin Song
Yuan Sun
Hua-Ji Qiu
Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities
Emerging Microbes and Infections
African swine fever virus
oxidative stress
Nrf2 signaling pathway
resveratrol
antiviral activity
title Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities
title_full Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities
title_fullStr Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities
title_full_unstemmed Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities
title_short Resveratrol inhibits African swine fever virus replication via the Nrf2-mediated reduced glutathione and antioxidative activities
title_sort resveratrol inhibits african swine fever virus replication via the nrf2 mediated reduced glutathione and antioxidative activities
topic African swine fever virus
oxidative stress
Nrf2 signaling pathway
resveratrol
antiviral activity
url https://www.tandfonline.com/doi/10.1080/22221751.2025.2469662
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