{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T17:08:39Z","timestamp":1763485719710,"version":"3.45.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation of State Key Laboratory of Component-based Chinese Medicine","award":["CBCM2024204"],"award-info":[{"award-number":["CBCM2024204"]}]},{"name":"Foundation of State Key Laboratory of Pathogen and Biosecurity of China","award":["SKLPBS2438"],"award-info":[{"award-number":["SKLPBS2438"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202492"],"award-info":[{"award-number":["82202492"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0712102"],"award-info":[{"award-number":["2020YFA0712102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["QNTD2023-01"],"award-info":[{"award-number":["QNTD2023-01"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nutrition and Care of Maternal & Child Research Project of Biostime Institute of Nutrition & Care","award":["2023BINCMCF28"],"award-info":[{"award-number":["2023BINCMCF28"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Human enteroviruses are important pathogens of hand-foot-and-mouth disease, poliomyelitis, and encephalitis, etc., posing substantial global health burdens with no specific approved therapeutics. While traditional Chinese medicine (TCM) has demonstrated antiviral potential during the COVID-19 pandemic, its efficacy and pharmacodynamic material basis against enteroviruses remains underexplored. Here, we systematically characterized the broad-spectrum anti-enterovirus activity of Huashi Baidu Formula (HSBDF), a clinically approved TCM for COVID-19, and identified three flavonoid compounds as its active components responsible for this antiviral effect. Transcriptomics analysis revealed that HSBDF attenuated CV-A9-induced inflammation by modulating MAPK and NF-\u03baB signaling pathways. High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS\/MS) analysis identified 152 chemical compounds in HSBDF, among which three flavonoids\u2014velutin, isorhamnetin, and (\u2212)-epicatechin gallate\u2014exhibited potent pan-enteroviral inhibition. Mechanistically, these compounds suppressed the activity of 3C proteases in enteroviruses, while concurrently attenuating CV-A9-induced upregulation of IL-6, TNF-\u03b1, MCP-1, and COX-2. Utilizing a BALB\/c young mouse model, it was demonstrated that the HSBDF and its compound velutin effectively suppressed viral replication in vivo. Collectively, this study advances TCM-based strategies for enterovirus therapy exemplified by HSBDF and highlights flavonoid scaffolds as promising candidates for developing broad-spectrum anti-enteroviral agents.<\/jats:p>","DOI":"10.3390\/biology14111615","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T16:49:51Z","timestamp":1763484591000},"page":"1615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HSBDF-Derived Bioactive Components Broadly Inhibit Enteroviruses by Targeting 3C Protease and Attenuating Inflammatory Responses"],"prefix":"10.3390","volume":"14","author":[{"given":"Ruolan","family":"Hu","sequence":"first","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Guan","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyue","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuxing","family":"Lou","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuqi","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehan","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3507-3969","authenticated-orcid":false,"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenlu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-8045","authenticated-orcid":false,"given":"Yigang","family":"Tong","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5007-2158","authenticated-orcid":false,"given":"Huahao","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tianjin University, Tianjin 300072, China"},{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China"},{"name":"State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"},{"name":"State Key Laboratory of Synthetic Biology, Tianjin University, Tianjin 300072, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2062-9903","authenticated-orcid":false,"given":"Bixia","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou 511436, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41579-018-0005-4","article-title":"The life cycle of non-polio enteroviruses and how to target it","volume":"16","author":"Baggen","year":"2018","journal-title":"Nat. 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