Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway

Enterovirus A71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus B3 (CVB3) are pathogenic members of the <i>Picornaviridae</i> family that cause a range of diseases, including severe central nervous system complications, myocarditis, and pancreatitis. Despite the considerable publi...

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Main Authors: Jae-Hyoung Song, Seo-Hyeon Mun, Heejung Yang, Yong Soo Kwon, Seong-Ryeol Kim, Min-young Song, Youngwook Ham, Hwa-Jung Choi, Won-Jin Baek, Sungchan Cho, Hyun-Jeong Ko
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Language:English
Published: MDPI AG 2023-12-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/16/1/16
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author Jae-Hyoung Song
Seo-Hyeon Mun
Heejung Yang
Yong Soo Kwon
Seong-Ryeol Kim
Min-young Song
Youngwook Ham
Hwa-Jung Choi
Won-Jin Baek
Sungchan Cho
Hyun-Jeong Ko
author_facet Jae-Hyoung Song
Seo-Hyeon Mun
Heejung Yang
Yong Soo Kwon
Seong-Ryeol Kim
Min-young Song
Youngwook Ham
Hwa-Jung Choi
Won-Jin Baek
Sungchan Cho
Hyun-Jeong Ko
author_sort Jae-Hyoung Song
collection DOAJ
description Enterovirus A71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus B3 (CVB3) are pathogenic members of the <i>Picornaviridae</i> family that cause a range of diseases, including severe central nervous system complications, myocarditis, and pancreatitis. Despite the considerable public health impact of these viruses, no approved antiviral treatments are currently available. In the present study, we confirmed the potential of saucerneol, a compound derived from <i>Saururus chinensis</i>, as an antiviral agent against EV71, CVA16, and CVB3. In the in vivo model, saucerneol effectively suppressed CVB3 replication in the pancreas and alleviated virus-induced pancreatitis. The antiviral activity of saucerneol is associated with increased mitochondrial ROS (mROS) production. In vitro inhibition of mROS generation diminishes the antiviral efficacy of saucerneol. Moreover, saucerneol treatment enhanced the phosphorylation of STING, TBK-1, and IRF3 in EV71- and CVA16-infected cells, indicating that its antiviral effects were mediated through the STING/TBK-1/IRF3 antiviral pathway, which was activated by increased mROS production. Saucerneol is a promising natural antiviral agent against EV71, CVA16, and CVB3 and has potential against virus-induced pancreatitis and myocarditis. Further studies are required to assess its safety and efficacy, which is essential for the development of effective antiviral strategies against these viruses.
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spelling doaj.art-a6f0f3865d9a4132a499f8a708cf67882024-01-26T18:46:41ZengMDPI AGViruses1999-49152023-12-011611610.3390/v16010016Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 PathwayJae-Hyoung Song0Seo-Hyeon Mun1Heejung Yang2Yong Soo Kwon3Seong-Ryeol Kim4Min-young Song5Youngwook Ham6Hwa-Jung Choi7Won-Jin Baek8Sungchan Cho9Hyun-Jeong Ko10Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of KoreaDepartment of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of KoreaDivision of Acute Viral Diseases, Centers for Emerging Virus Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Republic of KoreaDepartment of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of KoreaNucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of KoreaDepartment of Beauty Art, Youngsan University, 142 Bansong Beltway, Busan 48015, Republic of KoreaDepartment of Beauty Art, Youngsan University, 142 Bansong Beltway, Busan 48015, Republic of KoreaNucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of KoreaDepartment of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of KoreaEnterovirus A71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus B3 (CVB3) are pathogenic members of the <i>Picornaviridae</i> family that cause a range of diseases, including severe central nervous system complications, myocarditis, and pancreatitis. Despite the considerable public health impact of these viruses, no approved antiviral treatments are currently available. In the present study, we confirmed the potential of saucerneol, a compound derived from <i>Saururus chinensis</i>, as an antiviral agent against EV71, CVA16, and CVB3. In the in vivo model, saucerneol effectively suppressed CVB3 replication in the pancreas and alleviated virus-induced pancreatitis. The antiviral activity of saucerneol is associated with increased mitochondrial ROS (mROS) production. In vitro inhibition of mROS generation diminishes the antiviral efficacy of saucerneol. Moreover, saucerneol treatment enhanced the phosphorylation of STING, TBK-1, and IRF3 in EV71- and CVA16-infected cells, indicating that its antiviral effects were mediated through the STING/TBK-1/IRF3 antiviral pathway, which was activated by increased mROS production. Saucerneol is a promising natural antiviral agent against EV71, CVA16, and CVB3 and has potential against virus-induced pancreatitis and myocarditis. Further studies are required to assess its safety and efficacy, which is essential for the development of effective antiviral strategies against these viruses.https://www.mdpi.com/1999-4915/16/1/16enterovirus A71coxsackievirus A16saucerneolmitochondrial ROSantiviral
spellingShingle Jae-Hyoung Song
Seo-Hyeon Mun
Heejung Yang
Yong Soo Kwon
Seong-Ryeol Kim
Min-young Song
Youngwook Ham
Hwa-Jung Choi
Won-Jin Baek
Sungchan Cho
Hyun-Jeong Ko
Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway
Viruses
enterovirus A71
coxsackievirus A16
saucerneol
mitochondrial ROS
antiviral
title Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway
title_full Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway
title_fullStr Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway
title_full_unstemmed Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway
title_short Antiviral Mechanisms of Saucerneol from <i>Saururus chinensis</i> against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING/TKB-1/IRF3 Pathway
title_sort antiviral mechanisms of saucerneol from i saururus chinensis i against enterovirus a71 coxsackievirus a16 and coxsackievirus b3 role of mitochondrial ros and the sting tkb 1 irf3 pathway
topic enterovirus A71
coxsackievirus A16
saucerneol
mitochondrial ROS
antiviral
url https://www.mdpi.com/1999-4915/16/1/16
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