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 r...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(3CL^(pro)),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.展开更多
基金supported by the National Key Research and Development Program of China(2021YFE0201100 and 2022YFC0868300)the National Natural Science Foundation of China(22107004)。
文摘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(3CL^(pro)),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.
