Journal Article

HSBDF-Derived Bioactive Components Broadly Inhibit Enteroviruses by Targeting 3C Protease and Attenuating Inflammatory Responses

Lou, Fuxing, Liu, Chunlin, Li, Zhenlu, Zhang, Han, Jiang, Hongzheng, Wang, Yaxin, Pang, Zehan, Guan, Lin, Fan, Huahao, Hu, Ruolan, Tong, Yigang, Huang, Gang, Wang, Shuqi, Li, Siyue, Hong, Bixia

2025

Overview

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-κB signaling pathways. High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) analysis identified 152 chemical compounds in HSBDF, among which three flavonoids—velutin, isorhamnetin, and (−)-epicatechin gallate—exhibited 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-α, 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.

• Publisher: MDPI AG
• Subject: 3C protease inhibitor / anti-inflammatory / Antiviral activity / Antiviral agents / Antiviral drugs / Bioflavonoids / COVID-19 / COVID-19 vaccines / Disease transmission / Drug resistance / Encephalitis / enterovirus / Enteroviruses / Enzymes / Epicatechin / Epidemics / Ethylenediaminetetraacetic acid / Flavones / Flavonoids / Genes / Genomes / Hand-foot-and-mouth disease / Herbal medicine / High-performance liquid chromatography / Huashi Baidu Formula (HSBDF) / Inflammation / MAP kinase / Mass spectrometry / Mass spectroscopy / Medical research / Medicine, Botanic / Medicine, Chinese / Medicine, Herbal / Monocyte chemoattractant protein 1 / NF-κB protein / Pandemics / Pathogens / Pediatrics / Peptides / Pharmacodynamics / Plasmids / Poliomyelitis / Proteases / Public health / Scientific imaging / Traditional Chinese medicine / Transcriptomics / Tumor necrosis factor-α / Viral infections / Viruses / World health