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.

中文翻译：

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三寒化湿方及其生物活性化合物对COVID-19具有抗病毒和抗炎作用


三寒化湿方（SHHS）是一种中药（TCM），在临床上对2019冠状病毒病（COVID-19）显示出显着的治疗效果。但其具体机​​制和成分仍需进一步阐明。对感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的 Vero-E6 细胞进行的实验表明，SHHS 能有效抑制病毒侵袭和增殖。使用暴露于病毒样颗粒 (VLP) 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 阻碍了 SARS-CoV-2 的进入。尽管 SHHS 没有在受到 SARS-CoV-2 攻击的 K18-hACE2 小鼠中表现出直接的抗病毒作用，但它显着减轻了病理损伤并降低了趋化因子的表达，例如 C-C 基序配体 (CCL)-2、CCL-3、C –X–C 基序配体 (CXCL)-1、CXCL-6、CXCL-9、CXCL-10 和 CXCL-11 在肺部，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 降低炎症生物标志物水平的能力，包括白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子-α (TNF-α)。使用先进的分析技术，例如超高效液相色谱结合线性陷阱四极杆 Orbitrap 质谱 (UHPLC-LTQ-Orbitrap-MS) 和表面等离振子共振 (SPR)，nodakenin 被确定为 SHHS 的一种有效抗病毒成分，针对 3C类蛋白酶（3CL），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 还表现出显着的抗病毒作用，可将病毒载量降低 66% 以上。这项研究表明，SHHS 可以通过抑制病毒入侵和促进抗炎作用来对抗 COVID-19。