Background: The Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 coronavirus, remains a global threat despite lifting the health emergency. Scientists from all continents have been mobilized to d...Background: The Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 coronavirus, remains a global threat despite lifting the health emergency. Scientists from all continents have been mobilized to develop vaccines and medicines for prevention and cure. In Burkina Faso, traditional healers proposed using Scoparia dulcis L., a medicinal plant, to manage COVID-19. Method: In silico screening offers a quick drug-likeness evaluation of Scoparia dulcis L.-isolated biomolecules toward SARS-CoV-2 targets, such as Mpro protease. A review of the literature retrieved 35 biomolecules isolated from Scoparia dulcis. The potential interactions of these biomolecules with the amino acid residues of the SARS-CoV-2 Mpro protease were visualized. Affinities and probable oral route delivery were assessed using reference molecules such as remdesivir and nelfinavir. Results: The screening allowed the retention of 20 hit molecules, which had a better affinity for the target than the reference molecules remdesivir and nelfinavir, and analysis of the results identified height lead molecules with a significant interaction with the Mpro protease and being druggable. There are six flavonoids: cirsimarin, cynaroside, hydroxy-tetramethoxyflavone, gossypetin, luteolin, vitexin, one diterpene, glutinol, and one glycoside, eugenyl-glucoside. These molecules interact with methionine 6 and tyrosine 126 of SARS-CoV-2 Mpro. These two amino acids are essential for the dimerization of Mpro protease. Inhibitory action on Mpro protease can be expected from these biomolecules. Conclusion: Scoparia dulcis L. could help manage COVID-19 because it contains biomolecules that can inactivate SARS-CoV-2 Mpro.展开更多
In the twenty-first century,we have witnessed multiple coronavirus pandemics.Despite declining SARS-CoV-2 cases,continued research remains vital.We report the discovery of sydowiol B,a natural product,as a dual inhibi...In the twenty-first century,we have witnessed multiple coronavirus pandemics.Despite declining SARS-CoV-2 cases,continued research remains vital.We report the discovery of sydowiol B,a natural product,as a dual inhibitor of SARS-CoV-2 main protease(Mpro)and papain-like protease(PLpro).Sydowiol B interacts with the nano-channel at the Mpro dimer interface and the PLpro active site.Molecular dynamics simulations suggest that sydowiol B inhibits Mpro by limiting active site expansion rather than inducing collapse.Furthermore,sydowiol B binding may amplify the fluctuation of two loops coordinating with the structural Zn^(2+)in PLpro,displacing Zn^(2+)from the zinc finger domain to the S2 helix.Sydowiol B and its analogue,violaceol I,exhibit broad-spectrum antiviral activity against homologous coronaviruses.Given the conservation of Mpro and PLpro,sydowiol B and violaceol I are promising leads for designing and developing anti-coronavirus therapies.展开更多
目的:基于2019-nCoV冠状病毒3CL水解酶(3CL protease,Mpro)的三维结构,采用分子对接技术和网络药理学方法探寻祛肺毒一号方治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的物质基础和作用机制。方法:采用中药系统药理学数...目的:基于2019-nCoV冠状病毒3CL水解酶(3CL protease,Mpro)的三维结构,采用分子对接技术和网络药理学方法探寻祛肺毒一号方治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的物质基础和作用机制。方法:采用中药系统药理学数据库与分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)及文献检索搜集祛肺毒一号方组方中药的化学成分,并以类药性(drug likeness,DL)≥0.18及口服生物利用度(oral bioavailability,OB)≥30%为标准进行筛选,采用分子对接技术将筛选出的化合物与2019-nCoV 3CL Mpro对接,以结合能小于-9 kcal·mol^(-1)为标准,筛选祛肺毒一号方的活性成分。运用SwissTargetPrediction数据库预测活性成分的作用靶点,并在人类基因数据库(the human gene database,GeneCards)、美国国立生物技术信息中心(national center for biotechnology information,NCBI)数据库及CTD数据库检索COVID-19相关靶点,采用venny 2.1软件得到活性成分作用靶点与COVID-19相关靶点的交集靶点。将交集靶点导入STRING 11.0数据库,最终获得蛋白质相互作用网络图。采用DAVID数据库对交集靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。运用Cytoscape3.7.2软件构建“中药活性成分-疾病-通路-靶点”网络图。结果:通过检索TCMSP数据库与文献查找筛选出220个祛肺毒一号方的化学成分,以结合能≤-9 kcal·mol^(-1)为标准筛选得到33个活性成分,且结合能最低的3个化合物可共同作用于靶蛋白2019-nCoV 3CL Mpro。33个祛肺毒一号方活性成分的728个靶点与4165个COVID-19疾病相关靶点进行映射,最终得到祛肺毒一号方治疗COVID-19的有效靶点347个,核心靶点基因筛选得到CCR1、HCRTR2、MAPK3、BCL2L1等11个核心基因。KEGG通路富集显示靶点显著富集于磷酯酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(protein kinase B,Akt)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路、T细胞受体信号通路等179条通路。GO生物功能富集分析发现3210条GO生物功能,包括氧化应激反应、细胞对药物的反应等2871条生物过程,丝氨酸蛋白酶激酶活性、酪氨酸激酶活性等230条分子功能和膜筏、膜区等109条细胞组分。结论:祛肺毒一号方可能通过多成分调控多靶点、多通路防治新型冠状病毒肺炎。展开更多
我们仿效BBC的广播节目"60秒改进世界"(Sixty Second Idea to Improve the World)推出了"改进建筑60秒"栏目,每期将在世界范围内采访两位人物,请他们就建筑、城市、景观、技术等相关问题在60秒的时间里讲出一个或...我们仿效BBC的广播节目"60秒改进世界"(Sixty Second Idea to Improve the World)推出了"改进建筑60秒"栏目,每期将在世界范围内采访两位人物,请他们就建筑、城市、景观、技术等相关问题在60秒的时间里讲出一个或两个有启发性、批判性甚至有争议性的观点。本栏目如实记录了他们的话,采访所拍摄的视频将会出现在我们的相关网页上。所述观点只代表嘉宾本人,与本杂志立场无关。展开更多
H3N2, H5N1 and H5N8 virus were wide-spread epidemic in South Korea. Especially in 2014 Korea, the serious outbreak of avian influenza caused by H5N8 took place, effecting not only birds but also dogs. Antibody of H5N8...H3N2, H5N1 and H5N8 virus were wide-spread epidemic in South Korea. Especially in 2014 Korea, the serious outbreak of avian influenza caused by H5N8 took place, effecting not only birds but also dogs. Antibody of H5N8 virus was found on a dog which differentiated the virus from existing H3N2 canine virus. At this point, we wanted to find out why H5N8 was self-medicated in dogs and whether H5N8 would cross species boundaries and be fatal to dogs or other species. While H5N1 is avian influenza like H5N8, many cases of fatal infections among dogs caused by H5N1 have been reported. Another kind of avian influenza, H3N2 is most common type of canine influenza in Asia. With the use of decision tree and apriori algorithm, we could find out characteristics of H5N8 by comparing it with H5N1 and H3N2.展开更多
Despite the global decline in the severity of the coronavirus disease 2019(COVID-19)cases,the disease stillrepresents a major concern to the relevant scientific and medical communities.The primary concern of drug scie...Despite the global decline in the severity of the coronavirus disease 2019(COVID-19)cases,the disease stillrepresents a major concern to the relevant scientific and medical communities.The primary concern of drug scientists,virologists,and other concerned specialists in this respect is to find ready-to-use suitable and potent anticoronaviraltherapies that are broadly effective against the different species/strains of the coronaviruses in general,not only againstthe current and previous coronaviruses(e.g.,the recently-appeared severe acute respiratory syndrome coronavirus 2“SARS-CoV-2”),i.e.,effective antiviral agents for treatment and/or prophylaxis of any coronaviral infections,includingthose of the coming ones from the next species and strains(if any).As an expert in this field,I tried,in this up-to-dateperspective“viewpoint”article,to evaluate the suitability and applicability of using the currently-availableanticoronaviral agents for the next coronavirus diseases(COVIDs)and coronaviral pandemics,highlighting the mostimportant general guidelines that should be considered in the next pandemics from the therapeutic points of view.展开更多
文摘Background: The Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 coronavirus, remains a global threat despite lifting the health emergency. Scientists from all continents have been mobilized to develop vaccines and medicines for prevention and cure. In Burkina Faso, traditional healers proposed using Scoparia dulcis L., a medicinal plant, to manage COVID-19. Method: In silico screening offers a quick drug-likeness evaluation of Scoparia dulcis L.-isolated biomolecules toward SARS-CoV-2 targets, such as Mpro protease. A review of the literature retrieved 35 biomolecules isolated from Scoparia dulcis. The potential interactions of these biomolecules with the amino acid residues of the SARS-CoV-2 Mpro protease were visualized. Affinities and probable oral route delivery were assessed using reference molecules such as remdesivir and nelfinavir. Results: The screening allowed the retention of 20 hit molecules, which had a better affinity for the target than the reference molecules remdesivir and nelfinavir, and analysis of the results identified height lead molecules with a significant interaction with the Mpro protease and being druggable. There are six flavonoids: cirsimarin, cynaroside, hydroxy-tetramethoxyflavone, gossypetin, luteolin, vitexin, one diterpene, glutinol, and one glycoside, eugenyl-glucoside. These molecules interact with methionine 6 and tyrosine 126 of SARS-CoV-2 Mpro. These two amino acids are essential for the dimerization of Mpro protease. Inhibitory action on Mpro protease can be expected from these biomolecules. Conclusion: Scoparia dulcis L. could help manage COVID-19 because it contains biomolecules that can inactivate SARS-CoV-2 Mpro.
基金support by the Medical Subcenter of HUST Analytical&Testing Centersupported by the National Program for Support of Top-notch Young Professionals(No.0106514050)+4 种基金the National Natural Science Foundation of China(Nos.82273811 and U22A20380)the Hubei Provincial Natural Science Foundation of China(No.2024AFA028)the National Key Research and Development Program of China(No.2021YFA0910500)the Major Science and Technology Project of Hubei Province(No.2021ACA012)TongjiRongcheng Center for Biomedicine,Huazhong University of Science and Technology.
文摘In the twenty-first century,we have witnessed multiple coronavirus pandemics.Despite declining SARS-CoV-2 cases,continued research remains vital.We report the discovery of sydowiol B,a natural product,as a dual inhibitor of SARS-CoV-2 main protease(Mpro)and papain-like protease(PLpro).Sydowiol B interacts with the nano-channel at the Mpro dimer interface and the PLpro active site.Molecular dynamics simulations suggest that sydowiol B inhibits Mpro by limiting active site expansion rather than inducing collapse.Furthermore,sydowiol B binding may amplify the fluctuation of two loops coordinating with the structural Zn^(2+)in PLpro,displacing Zn^(2+)from the zinc finger domain to the S2 helix.Sydowiol B and its analogue,violaceol I,exhibit broad-spectrum antiviral activity against homologous coronaviruses.Given the conservation of Mpro and PLpro,sydowiol B and violaceol I are promising leads for designing and developing anti-coronavirus therapies.
文摘目的:基于2019-nCoV冠状病毒3CL水解酶(3CL protease,Mpro)的三维结构,采用分子对接技术和网络药理学方法探寻祛肺毒一号方治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的物质基础和作用机制。方法:采用中药系统药理学数据库与分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)及文献检索搜集祛肺毒一号方组方中药的化学成分,并以类药性(drug likeness,DL)≥0.18及口服生物利用度(oral bioavailability,OB)≥30%为标准进行筛选,采用分子对接技术将筛选出的化合物与2019-nCoV 3CL Mpro对接,以结合能小于-9 kcal·mol^(-1)为标准,筛选祛肺毒一号方的活性成分。运用SwissTargetPrediction数据库预测活性成分的作用靶点,并在人类基因数据库(the human gene database,GeneCards)、美国国立生物技术信息中心(national center for biotechnology information,NCBI)数据库及CTD数据库检索COVID-19相关靶点,采用venny 2.1软件得到活性成分作用靶点与COVID-19相关靶点的交集靶点。将交集靶点导入STRING 11.0数据库,最终获得蛋白质相互作用网络图。采用DAVID数据库对交集靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。运用Cytoscape3.7.2软件构建“中药活性成分-疾病-通路-靶点”网络图。结果:通过检索TCMSP数据库与文献查找筛选出220个祛肺毒一号方的化学成分,以结合能≤-9 kcal·mol^(-1)为标准筛选得到33个活性成分,且结合能最低的3个化合物可共同作用于靶蛋白2019-nCoV 3CL Mpro。33个祛肺毒一号方活性成分的728个靶点与4165个COVID-19疾病相关靶点进行映射,最终得到祛肺毒一号方治疗COVID-19的有效靶点347个,核心靶点基因筛选得到CCR1、HCRTR2、MAPK3、BCL2L1等11个核心基因。KEGG通路富集显示靶点显著富集于磷酯酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(protein kinase B,Akt)信号通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路、T细胞受体信号通路等179条通路。GO生物功能富集分析发现3210条GO生物功能,包括氧化应激反应、细胞对药物的反应等2871条生物过程,丝氨酸蛋白酶激酶活性、酪氨酸激酶活性等230条分子功能和膜筏、膜区等109条细胞组分。结论:祛肺毒一号方可能通过多成分调控多靶点、多通路防治新型冠状病毒肺炎。
文摘我们仿效BBC的广播节目"60秒改进世界"(Sixty Second Idea to Improve the World)推出了"改进建筑60秒"栏目,每期将在世界范围内采访两位人物,请他们就建筑、城市、景观、技术等相关问题在60秒的时间里讲出一个或两个有启发性、批判性甚至有争议性的观点。本栏目如实记录了他们的话,采访所拍摄的视频将会出现在我们的相关网页上。所述观点只代表嘉宾本人,与本杂志立场无关。
文摘H3N2, H5N1 and H5N8 virus were wide-spread epidemic in South Korea. Especially in 2014 Korea, the serious outbreak of avian influenza caused by H5N8 took place, effecting not only birds but also dogs. Antibody of H5N8 virus was found on a dog which differentiated the virus from existing H3N2 canine virus. At this point, we wanted to find out why H5N8 was self-medicated in dogs and whether H5N8 would cross species boundaries and be fatal to dogs or other species. While H5N1 is avian influenza like H5N8, many cases of fatal infections among dogs caused by H5N1 have been reported. Another kind of avian influenza, H3N2 is most common type of canine influenza in Asia. With the use of decision tree and apriori algorithm, we could find out characteristics of H5N8 by comparing it with H5N1 and H3N2.
文摘Despite the global decline in the severity of the coronavirus disease 2019(COVID-19)cases,the disease stillrepresents a major concern to the relevant scientific and medical communities.The primary concern of drug scientists,virologists,and other concerned specialists in this respect is to find ready-to-use suitable and potent anticoronaviraltherapies that are broadly effective against the different species/strains of the coronaviruses in general,not only againstthe current and previous coronaviruses(e.g.,the recently-appeared severe acute respiratory syndrome coronavirus 2“SARS-CoV-2”),i.e.,effective antiviral agents for treatment and/or prophylaxis of any coronaviral infections,includingthose of the coming ones from the next species and strains(if any).As an expert in this field,I tried,in this up-to-dateperspective“viewpoint”article,to evaluate the suitability and applicability of using the currently-availableanticoronaviral agents for the next coronavirus diseases(COVIDs)and coronaviral pandemics,highlighting the mostimportant general guidelines that should be considered in the next pandemics from the therapeutic points of view.
