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Sanhan Huashi Formula and Its Bioactive Compounds Exert Antiviral and Anti-Inflammatory Effects on COVID-19

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Title: Sanhan Huashi Formula and Its Bioactive Compounds Exert Antiviral and Anti-Inflammatory Effects on COVID-19
Authors: Chuanxi Tian, Hang Liu, Qian Wang, Jinyue Zhao, Chensi Yao, Yanfeng Yao, Xu Zhang, Qinhai Ma, Weihao Wang, Yanyan Zhou, Mengxiao Wang, Xiaomeng Shi, Xiangyan Li, Shan Wang, Yingying Yang, Xiaowen Gou, Lijuan Zhou, Jingyi Zhao, Li Wan, Jiarui Li, Stefanie Tiefenbacher, Juntao Gao, Rudolf Bauer, Min Li, Xiaolin Tong
Source: Engineering, Vol 43, Iss , Pp 159-172 (2024)
Publisher Information: Elsevier, 2024.
Publication Year: 2024
Collection: LCC:Engineering (General). Civil engineering (General)
Subject Terms: Sanhan Huashi formula, Coronavirus disease 2019, Anti-inflammatory properties, Nodakenin, 3C-like protease, Engineering (General). Civil engineering (General), TA1-2040
More Details: Sanhan Huashi formula (SHHS), a traditional Chinese medicine (TCM), has shown significant therapeutic effects on coronavirus disease 2019 (COVID-19) in clinical settings. However, its specific mechanism and components still require further clarification. In vitro experiments with Vero-E6 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrated that SHHS effectively inhibited viral invasion and proliferation. Complementary in vivo experiments using K18-human angiotensin converting enzyme 2 (hACE2) mice exposed to virus-like particles (VLPs) further confirmed that SHHS impeded SARS-CoV-2 entry. Although SHHS did not demonstrate direct antiviral effects in K18-hACE2 mice challenged with SARS-CoV-2, it significantly alleviated pathological damage and decreased the expression of chemokines such as C–C motif ligand (CCL)-2, CCL-3, C–X–C motif ligand (CXCL)-1, CXCL-6, CXCL-9, CXCL-10, and CXCL-11 in the lungs, suggesting that SHHS exerts immunomodulatory and anti-inflammatory effects via the CCL-2–CXCL axis. Additional research using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) and RAW264.7 cell model validated the ability of SHHS to reduce the levels of inflammatory biomarkers, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Using advanced analytical techniques such as ultrahigh-performance liquid chromatography coupled with linear trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) and surface plasmon resonance (SPR), nodakenin was identified as a potent antiviral component of SHHS that targets the 3C-like protease (3CLpro), a finding supported by the hydrogen–deuterium exchange mass spectrometry (HDX-MS) and molecular docking analyses. Furthermore, nodakenin demonstrated a significant antiviral effect, reducing the viral load by more than 66%. This investigation reveals that SHHS can combat COVID-19 by inhibiting viral invasion and promoting anti-inflammatory effects.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2095-8099
Relation: http://www.sciencedirect.com/science/article/pii/S2095809924003965; https://doaj.org/toc/2095-8099
DOI: 10.1016/j.eng.2024.07.007
Access URL: https://doaj.org/article/7dd8ba20fee747ebb185f9caf9e8280a
Accession Number: edsdoj.7dd8ba20fee747ebb185f9caf9e8280a
Database: Directory of Open Access Journals
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  Data: Sanhan Huashi formula (SHHS), a traditional Chinese medicine (TCM), has shown significant therapeutic effects on coronavirus disease 2019 (COVID-19) in clinical settings. However, its specific mechanism and components still require further clarification. In vitro experiments with Vero-E6 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrated that SHHS effectively inhibited viral invasion and proliferation. Complementary in vivo experiments using K18-human angiotensin converting enzyme 2 (hACE2) mice exposed to virus-like particles (VLPs) further confirmed that SHHS impeded SARS-CoV-2 entry. Although SHHS did not demonstrate direct antiviral effects in K18-hACE2 mice challenged with SARS-CoV-2, it significantly alleviated pathological damage and decreased the expression of chemokines such as C–C motif ligand (CCL)-2, CCL-3, C–X–C motif ligand (CXCL)-1, CXCL-6, CXCL-9, CXCL-10, and CXCL-11 in the lungs, suggesting that SHHS exerts immunomodulatory and anti-inflammatory effects via the CCL-2–CXCL axis. Additional research using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) and RAW264.7 cell model validated the ability of SHHS to reduce the levels of inflammatory biomarkers, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Using advanced analytical techniques such as ultrahigh-performance liquid chromatography coupled with linear trap quadrupole Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) and surface plasmon resonance (SPR), nodakenin was identified as a potent antiviral component of SHHS that targets the 3C-like protease (3CLpro), a finding supported by the hydrogen–deuterium exchange mass spectrometry (HDX-MS) and molecular docking analyses. Furthermore, nodakenin demonstrated a significant antiviral effect, reducing the viral load by more than 66%. This investigation reveals that SHHS can combat COVID-19 by inhibiting viral invasion and promoting anti-inflammatory effects.
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