Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role i...Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.展开更多
This paper presented empirical models of describing reaction rate vs. hydrochloric acid temperature and concentration by regressing experimental data. And this paper also introduced the dependent reaction heat model i...This paper presented empirical models of describing reaction rate vs. hydrochloric acid temperature and concentration by regressing experimental data. And this paper also introduced the dependent reaction heat model into the thermal non-equilibrium models and coupled with two-scale continuum model to obtain governing equations for describing wormholing under non-isothermal conditions. The governing equations were discretized by implicit difference method and solved by programing. The effects of temperature on wormholing have been investigated based on the simulation results on 2-D vision. A significant difference of the effluent temperature between the dependent reaction heat model in present work and the constant reaction heat model in available literatures was observed, especially in high injection rate and strong acid concentration. In addition, the tendencies of optimum injection capacity vs. injection temperature under isothermal and non-isothermal conditions were almost different. Finally, an optimum injection temperature was found by changing the injection temperature under non-isothermal conditions.展开更多
It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and ...It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.展开更多
To the Editor： A frail 74-year-old woman visited the emergency department with a chief complaint of＂intermittent abdominal pain for 6 days and vomiting for 2 days＂. She described her symptoms as a colicky lower abd...To the Editor： A frail 74-year-old woman visited the emergency department with a chief complaint of＂intermittent abdominal pain for 6 days and vomiting for 2 days＂. She described her symptoms as a colicky lower abdominal pain that occurred 6 days ago, recurred several times, and resolved spontaneously, but progressed to severe and sustained pain with vomiting 2 days bet＇ore visiting the hospital. The lower abdominal pain also radiated down to the right medial thigh. Physical examination of the abdomen revealed distention, with intestinal pattern and positive bowel sounds. Tenderness on tile lower abdomen was identified, which radiated to the right medial thigh. There was no palpable mass in the abdominal or groin area.展开更多
基金supported by National Natural Science Foundation of China(Grant Nos.:81891010/81891011,81725023,82003614,82173950,31770192,32070187,32161133003 and 82003681)China Postdoctoral Science Foundation(Grant No:2022T150029).
文摘Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
基金supported by grants from the National Natural Science Foundation of China,No.51474182International Science and Technology Cooperation Research Program of Sichuan Province(China)under Grant,No.2017HH0014.
文摘This paper presented empirical models of describing reaction rate vs. hydrochloric acid temperature and concentration by regressing experimental data. And this paper also introduced the dependent reaction heat model into the thermal non-equilibrium models and coupled with two-scale continuum model to obtain governing equations for describing wormholing under non-isothermal conditions. The governing equations were discretized by implicit difference method and solved by programing. The effects of temperature on wormholing have been investigated based on the simulation results on 2-D vision. A significant difference of the effluent temperature between the dependent reaction heat model in present work and the constant reaction heat model in available literatures was observed, especially in high injection rate and strong acid concentration. In addition, the tendencies of optimum injection capacity vs. injection temperature under isothermal and non-isothermal conditions were almost different. Finally, an optimum injection temperature was found by changing the injection temperature under non-isothermal conditions.
基金supported by National Natural Science Foundation of China(Nos.81891010/81891011,81725023,82003614,82173950,31770192,32070187 and 82003681)China Postdoctoral Science Foundation(2022T150029,China)+1 种基金the National Key Research and Development Program of China(No.2017-YFC1700405)the Science&Technology Department of Xinjiang Uygur Autonomous Region(2018AB012,China)。
文摘It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.
文摘To the Editor： A frail 74-year-old woman visited the emergency department with a chief complaint of＂intermittent abdominal pain for 6 days and vomiting for 2 days＂. She described her symptoms as a colicky lower abdominal pain that occurred 6 days ago, recurred several times, and resolved spontaneously, but progressed to severe and sustained pain with vomiting 2 days bet＇ore visiting the hospital. The lower abdominal pain also radiated down to the right medial thigh. Physical examination of the abdomen revealed distention, with intestinal pattern and positive bowel sounds. Tenderness on tile lower abdomen was identified, which radiated to the right medial thigh. There was no palpable mass in the abdominal or groin area.
