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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 Saururus chinensis, 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.<\/jats:p>","DOI":"10.3390\/v16010016","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T08:16:02Z","timestamp":1703146562000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antiviral Mechanisms of Saucerneol from Saururus chinensis against Enterovirus A71, Coxsackievirus A16, and Coxsackievirus B3: Role of Mitochondrial ROS and the STING\/TKB-1\/IRF3 Pathway"],"prefix":"10.3390","volume":"16","author":[{"given":"Jae-Hyoung","family":"Song","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"},{"name":"Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Hyeon","family":"Mun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-9024","authenticated-orcid":false,"given":"Heejung","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Soo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Ryeol","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Acute Viral Diseases, Centers for Emerging Virus Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju 28159, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-young","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngwook","family":"Ham","sequence":"additional","affiliation":[{"name":"Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"},{"name":"Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (KUST), Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa-Jung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Beauty Art, Youngsan University, 142 Bansong Beltway, Busan 48015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Jin","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Beauty Art, Youngsan University, 142 Bansong Beltway, Busan 48015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7627-978X","authenticated-orcid":false,"given":"Sungchan","family":"Cho","sequence":"additional","affiliation":[{"name":"Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea"},{"name":"Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology (KUST), Daejeon 34113, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3844-928X","authenticated-orcid":false,"given":"Hyun-Jeong","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"},{"name":"Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10319","DOI":"10.1128\/JVI.00787-11","article-title":"Enterovirus 71 and coxsackievirus A16 3C proteases: Binding to rupintrivir and their substrates and anti-hand, foot, and mouth disease virus drug design","volume":"85","author":"Lu","year":"2011","journal-title":"J. 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