Background:The outbreak of coronavirus disease 2019(COVID-19)has caused a public catastrophe and global concern.The main symptoms of COVID-19 are fever,cough,myalgia,fatigue and lower respiratory tract infection signs...Background:The outbreak of coronavirus disease 2019(COVID-19)has caused a public catastrophe and global concern.The main symptoms of COVID-19 are fever,cough,myalgia,fatigue and lower respiratory tract infection signs.Almost all populations are susceptible to the virus,and thebasic reproduction number(R0)is 2.8-3.9.The fight against COVID-19 should have two aspects:one is the treatment of infected patients,and the other is the mobilization of the society to avoid the spread of the virus.The treatment of patients includes supportive treatment,antiviral treatment,and oxygen therapy.For patients with severe acute respiratory distress syndrome(ARDS),extracorporeal membrane oxygenation(ECMO)and circulatory support are recommended.Plasma therapy and traditional Chinese medicine have also achieved good outcomes.This review is intended to summarize the research on this new coronavirus,to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS)and to provide guidance regarding new methods of prevention,diagnosis and clinical treatment based on autodock simulations.Methods:This review compares the multifaceted characteristics of the three coronaviruses including COVID-19,SARS and MERS.Our researchers take the COVID-19,SARS,and MERS as key words and search literatures in the Pubmed database.We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses.Results:We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2,SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S.We also found that the types and severity of clinical symptoms vary,which means that the diagnosis and nursing measures also require differentiation.In addition to the common route of transmission including airborne transmission,these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19.Conclusions:In evolutionary history,these three coronaviruses have some similar biological features as well as some different mutational characteristics.Their receptors and routes of transmission are not all the same,which makes them different in clinical features and treatments.We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2,such as remdesivir,chloroquine,ciclesonide and niclosamide,and may be a potential target in COVID-19.展开更多
目的:利用反向对接技术以大黄酸为研究对象筛选出大黄酸的炎症靶标蛋白。方法:获取Toll样受体/核因子(4TLR4/NF-κB)、p38促分裂原活化蛋白激酶(P38mitogen-activated protein kinases,P38 MAKP)和Janus激酶-信号转导转录激活因子(Janus...目的:利用反向对接技术以大黄酸为研究对象筛选出大黄酸的炎症靶标蛋白。方法:获取Toll样受体/核因子(4TLR4/NF-κB)、p38促分裂原活化蛋白激酶(P38mitogen-activated protein kinases,P38 MAKP)和Janus激酶-信号转导转录激活因子(Janus kinase 2/signal transducer and activator of transcription 3,JAK2/STAT3)3条炎症通路上的30个蛋白的晶体学结构以及大黄酸的化学结构;利用AutoDockTools对所有晶体学结构进行标准化处理;通过AutoGrid对靶标蛋白的活性位点进行计算;利用AutoDock对大黄酸进行反向对接模拟实验;对得到的对接结果进行筛选,根据对接自由能的高低,筛选出亲和力高的靶蛋白;对筛选得到的靶蛋白进行作用力分析并作图。结果:反向筛选得到3个与大黄酸具有高亲和性的靶蛋白,分别为P38、PI3Kγ、JAK2。结论:大黄酸是通过抑制P38、PI3Kγ、JAK2靶蛋白,进而阻碍炎症信号传递,影响下游蛋白的表达,发挥抗炎作用。展开更多
基金supported by the Major State Basic Research Development Program of China (973 Program) (No.2005CB523401,No.2006CB504703)national special funds for scientific research on public causes (No.200707010)~~
基金This research was funded by the National Key Research and Development Program of China(2018YFA0108700)the NSFC Projects of International Cooperation and Exchanges(81720102004)the National Natural Science Foundation of China(81974019,81970248).
文摘Background:The outbreak of coronavirus disease 2019(COVID-19)has caused a public catastrophe and global concern.The main symptoms of COVID-19 are fever,cough,myalgia,fatigue and lower respiratory tract infection signs.Almost all populations are susceptible to the virus,and thebasic reproduction number(R0)is 2.8-3.9.The fight against COVID-19 should have two aspects:one is the treatment of infected patients,and the other is the mobilization of the society to avoid the spread of the virus.The treatment of patients includes supportive treatment,antiviral treatment,and oxygen therapy.For patients with severe acute respiratory distress syndrome(ARDS),extracorporeal membrane oxygenation(ECMO)and circulatory support are recommended.Plasma therapy and traditional Chinese medicine have also achieved good outcomes.This review is intended to summarize the research on this new coronavirus,to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS)and to provide guidance regarding new methods of prevention,diagnosis and clinical treatment based on autodock simulations.Methods:This review compares the multifaceted characteristics of the three coronaviruses including COVID-19,SARS and MERS.Our researchers take the COVID-19,SARS,and MERS as key words and search literatures in the Pubmed database.We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses.Results:We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2,SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S.We also found that the types and severity of clinical symptoms vary,which means that the diagnosis and nursing measures also require differentiation.In addition to the common route of transmission including airborne transmission,these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19.Conclusions:In evolutionary history,these three coronaviruses have some similar biological features as well as some different mutational characteristics.Their receptors and routes of transmission are not all the same,which makes them different in clinical features and treatments.We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2,such as remdesivir,chloroquine,ciclesonide and niclosamide,and may be a potential target in COVID-19.
文摘目的:利用反向对接技术以大黄酸为研究对象筛选出大黄酸的炎症靶标蛋白。方法:获取Toll样受体/核因子(4TLR4/NF-κB)、p38促分裂原活化蛋白激酶(P38mitogen-activated protein kinases,P38 MAKP)和Janus激酶-信号转导转录激活因子(Janus kinase 2/signal transducer and activator of transcription 3,JAK2/STAT3)3条炎症通路上的30个蛋白的晶体学结构以及大黄酸的化学结构;利用AutoDockTools对所有晶体学结构进行标准化处理;通过AutoGrid对靶标蛋白的活性位点进行计算;利用AutoDock对大黄酸进行反向对接模拟实验;对得到的对接结果进行筛选,根据对接自由能的高低,筛选出亲和力高的靶蛋白;对筛选得到的靶蛋白进行作用力分析并作图。结果:反向筛选得到3个与大黄酸具有高亲和性的靶蛋白,分别为P38、PI3Kγ、JAK2。结论:大黄酸是通过抑制P38、PI3Kγ、JAK2靶蛋白,进而阻碍炎症信号传递,影响下游蛋白的表达,发挥抗炎作用。
