三汗化石配方及其生物活性化合物对 COVID-19 具有抗病毒和抗炎作用

IF 10.1 1区工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY

Engineering Pub Date : 2024-07-24 DOI:10.1016/j.eng.2024.07.007

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

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Complementary 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). 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引用次数: 0

摘要

中药三味化石散（SHHS）在临床上对冠状病毒病2019（COVID-19）有显著疗效。用感染严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）的 Vero-E6 细胞进行的实验表明，SHHS 能有效抑制病毒的入侵和增殖。使用暴露于病毒样颗粒（VLPs）的 K18-人血管紧张素转换酶 2（hACE2）小鼠进行的补充实验进一步证实，SHHS 可阻止 SARS-CoV-2 进入。虽然 SHHS 在受到 SARS-CoV-2 挑战的 K18-hACE2 小鼠中没有显示出直接的抗病毒作用，但它显著减轻了病理损伤，并降低了肺中 C-C motif ligand (CCL)-2、CCL-3、C-X-C motif ligand (CXCL)-1、CXCL-6、CXCL-9、CXCL-10 和 CXCL-11 等趋化因子的表达，表明 SHHS 通过 CCL-2-CXCL 轴发挥免疫调节和抗炎作用。使用脂多糖（LPS）诱导的急性肺损伤（ALI）和 RAW264.7 细胞模型进行的其他研究验证了 SHHS 降低白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子-α（TNF-α）等炎症生物标志物水平的能力。利用超高效液相色谱-线性阱四极杆 Orbitrap 质谱（UHPLC-LTQ-Orbitrap-MS）和表面等离子体共振（SPR）等先进分析技术，研究人员发现，nodakenin 是 SHHS 中一种针对 3C 样蛋白酶（3CL）的强效抗病毒成分，这一发现得到了氢氘交换质谱（HDX-MS）和分子对接分析的支持。此外，nodakenin 还具有显著的抗病毒效果，可将病毒载量降低 66% 以上。这项研究揭示了 SHHS 可以通过抑制病毒入侵和促进抗炎作用来对抗 COVID-19。

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

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. 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 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 (3CL), 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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来源期刊

Engineering Environmental Science-Environmental Engineering

自引率

1.60%

发文量

335

审稿时长

35 days

期刊介绍： Engineering, an international open-access journal initiated by the Chinese Academy of Engineering (CAE) in 2015, serves as a distinguished platform for disseminating cutting-edge advancements in engineering R&D, sharing major research outputs, and highlighting key achievements worldwide. The journal's objectives encompass reporting progress in engineering science, fostering discussions on hot topics, addressing areas of interest, challenges, and prospects in engineering development, while considering human and environmental well-being and ethics in engineering. It aims to inspire breakthroughs and innovations with profound economic and social significance, propelling them to advanced international standards and transforming them into a new productive force. Ultimately, this endeavor seeks to bring about positive changes globally, benefit humanity, and shape a new future.