Coronavirus disease 2019 is threatening thousands of millions of people around the world.In the absence of specific and highly effective medicines,the treatment of infected persons is still very challenging.As therape...Coronavirus disease 2019 is threatening thousands of millions of people around the world.In the absence of specific and highly effective medicines,the treatment of infected persons is still very challenging.As therapeutics,neutralizing antibodies(NAbs)have great potential.Many NAbs have been reported,and most target various regions on the receptor-binding domain of the spike(S)protein,or the N-terminal domain.Several NAbs and NAb cocktails have been authorized for emergency use,and more arc in clinical trials or are under development.In this review,considering the angle of binding epitopes on the S protein,we summarize the functions and the underlying mechanisms of a set of well-recognized NAbs and provide guidance for vaccine design and the combinatorial use of these antibodies.In addition,we review the NAbs and NAb cocktails that have been approved for emergency use and discuss the effectiveness of these NAbs for combating severe acute respiratory syndrome coronavirus 2 mutants.展开更多
Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are ...Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.展开更多
The COVID-19 pandemic,caused by SARS-CoV-2,has presented an unprecedented challenge to global public health.The rapid,reliable,and affordable diagnosis of COVID-19 is essential for controlling the spread of the acute ...The COVID-19 pandemic,caused by SARS-CoV-2,has presented an unprecedented challenge to global public health.The rapid,reliable,and affordable diagnosis of COVID-19 is essential for controlling the spread of the acute disease[1].The nucleic acid test(NAT)is the gold standard for diagnosing COVID-19 due to its high sensitivity and accuracy[1].Although NAT yields clinically actionable information,false-negative results often occur,especially when sample collection is not performed appropriately[2].To complement NAT,serological testing is essential for the rapid detection and monitoring of mild or asymptomatic infections[1].Serological tests provide valuable information for improving diagnosis,including the estimation of population exposure,disease severity,and clinical outcomes[1].展开更多
Serological tests play an essential role in monitoring and combating the COVID-19 pandemic.Recombinant spike protein(S protein),especially the S1 protein,is one of the major reagents used for serological tests.However...Serological tests play an essential role in monitoring and combating the COVID-19 pandemic.Recombinant spike protein(S protein),especially the S1 protein,is one of the major reagents used for serological tests.However,the high cost of S protein production and possible cross-reactivity with other human coronaviruses pose unavoidable challenges.By taking advantage of a peptide microarray with full spike protein coverage,we analyzed 2,434 sera from 858 COVID-19 patients,63 asymptomatic patients and 610 controls collected from multiple clinical centers.Based on the results,we identified several S protein-derived 12-mer peptides that have high diagnostic performance.In particular,for monitoring the IgG response,one peptide(aa 1148-1159 or S2-78)exhibited a sensitivity(95.5%,95%CI 93.7-96.9%)and specificity(96.7%,95%CI 94.8-98.0%)comparable to those of the S1 protein for the detection of both symptomatic and asymptomatic COVID-19 cases.Furthermore,the diagnostic performance of the S2-78(aa 1148-1159)IgG was successfully validated by ELISA in an independent sample cohort.A panel of four peptides,S1-93(aa 553-564),S1-97(aa 577-588),S1-101(aa 601-612)and S1-105(aa 625-636),that likely will avoid potential cross-reactivity with sera from patients infected by other coronaviruses was constructed.The peptides identified in this study may be applied independently or in combination with the S1 protein for accurate,affordable,and accessible COVID-19 diagnosis.展开更多
There is a worldwide pandemic of COVID-19 caused by SARS-CoV-2.1 By January 28,2021,more than 100 million cases had been diagnosed,and more than 2 million deaths had been reported(https://coronavirus.jhu.edu/map.html)...There is a worldwide pandemic of COVID-19 caused by SARS-CoV-2.1 By January 28,2021,more than 100 million cases had been diagnosed,and more than 2 million deaths had been reported(https://coronavirus.jhu.edu/map.html).The comprehensive and in-depth elucidation of SARS-CoV-2-specific IgG responses will help us to better understand COVID-19 immunity and facilitate the precise development of neutralizing antibodies and vaccines.展开更多
Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COV...Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the“START”button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.展开更多
Background:To study the effects of cryopreservation on human sperm glycocalyx.Methods:The lectin binding profilings of sperm after freeze-thaw were compared by lectin microarray.Results:CryoSperm^(TM) and direct fumig...Background:To study the effects of cryopreservation on human sperm glycocalyx.Methods:The lectin binding profilings of sperm after freeze-thaw were compared by lectin microarray.Results:CryoSperm^(TM) and direct fumigation were confirmed to be the optimized cryoprotectant and method by comparing the sperm recovery rate.In 91 lectins,33 lectins were significantly changed after sperm cryopreservation.Among them,9 lectins greatly decreased and 24 lectins mainly increased.The binding signals of MAA,PSA,ABA,and AIA were verified by FACS,and the results were consistent with that of lectin microarray.Conclusions:Sperm glycocalyx had significant changes after cryopreservation.The sialic acid,playing an important role in protecting sperm,was greatly lost,which exposed the inner carbohydrates.Thus,the glycocalyx damage due to the cryopreservation might be one of the reasons for low sperm fertility.展开更多
基金supported by the National Natural Science Foundation of China(Nos.31970130,31600672,31670831,and 31370813).
文摘Coronavirus disease 2019 is threatening thousands of millions of people around the world.In the absence of specific and highly effective medicines,the treatment of infected persons is still very challenging.As therapeutics,neutralizing antibodies(NAbs)have great potential.Many NAbs have been reported,and most target various regions on the receptor-binding domain of the spike(S)protein,or the N-terminal domain.Several NAbs and NAb cocktails have been authorized for emergency use,and more arc in clinical trials or are under development.In this review,considering the angle of binding epitopes on the S protein,we summarize the functions and the underlying mechanisms of a set of well-recognized NAbs and provide guidance for vaccine design and the combinatorial use of these antibodies.In addition,we review the NAbs and NAb cocktails that have been approved for emergency use and discuss the effectiveness of these NAbs for combating severe acute respiratory syndrome coronavirus 2 mutants.
基金supported by the National Key Research and Development Program of China(2020YFE0202200)the National Natural Science Foundation of China(31900112,21907065,31970130 and 31670831)。
文摘Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.
基金the National Key Research and Development Program of China Grant(No.2020YFE0202200)the National Natural Science Foundation of China(Nos.31900112 and 31970130).
文摘The COVID-19 pandemic,caused by SARS-CoV-2,has presented an unprecedented challenge to global public health.The rapid,reliable,and affordable diagnosis of COVID-19 is essential for controlling the spread of the acute disease[1].The nucleic acid test(NAT)is the gold standard for diagnosing COVID-19 due to its high sensitivity and accuracy[1].Although NAT yields clinically actionable information,false-negative results often occur,especially when sample collection is not performed appropriately[2].To complement NAT,serological testing is essential for the rapid detection and monitoring of mild or asymptomatic infections[1].Serological tests provide valuable information for improving diagnosis,including the estimation of population exposure,disease severity,and clinical outcomes[1].
基金supported by National Key Research and Development Program of China Grant(No.2016YFA0500600)Science and Technology Commission of Shanghai Municipality(No.19441911900)+1 种基金Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2020YQ10)the National Natural Science Foundation of China(No.31900112,21907065,31970130,and 31670831).
文摘Serological tests play an essential role in monitoring and combating the COVID-19 pandemic.Recombinant spike protein(S protein),especially the S1 protein,is one of the major reagents used for serological tests.However,the high cost of S protein production and possible cross-reactivity with other human coronaviruses pose unavoidable challenges.By taking advantage of a peptide microarray with full spike protein coverage,we analyzed 2,434 sera from 858 COVID-19 patients,63 asymptomatic patients and 610 controls collected from multiple clinical centers.Based on the results,we identified several S protein-derived 12-mer peptides that have high diagnostic performance.In particular,for monitoring the IgG response,one peptide(aa 1148-1159 or S2-78)exhibited a sensitivity(95.5%,95%CI 93.7-96.9%)and specificity(96.7%,95%CI 94.8-98.0%)comparable to those of the S1 protein for the detection of both symptomatic and asymptomatic COVID-19 cases.Furthermore,the diagnostic performance of the S2-78(aa 1148-1159)IgG was successfully validated by ELISA in an independent sample cohort.A panel of four peptides,S1-93(aa 553-564),S1-97(aa 577-588),S1-101(aa 601-612)and S1-105(aa 625-636),that likely will avoid potential cross-reactivity with sera from patients infected by other coronaviruses was constructed.The peptides identified in this study may be applied independently or in combination with the S1 protein for accurate,affordable,and accessible COVID-19 diagnosis.
基金partially supported by National Key Research and Developm ent Program of China Grant(No.2016YFA0500600)National Natural Science Foundation of China(Nos.31970130,31670831,31370813,and 31501054)Open Foundation of Key Laboratory of Systems Biomedicine(No.KLSB2020QN-05).
文摘There is a worldwide pandemic of COVID-19 caused by SARS-CoV-2.1 By January 28,2021,more than 100 million cases had been diagnosed,and more than 2 million deaths had been reported(https://coronavirus.jhu.edu/map.html).The comprehensive and in-depth elucidation of SARS-CoV-2-specific IgG responses will help us to better understand COVID-19 immunity and facilitate the precise development of neutralizing antibodies and vaccines.
基金partially supported by the National Key R&D Program of China Grant(Grant No.2016YFA0500600)the National Natural Science Foundation of China(Grant Nos.31970130,31600672,31900112,21907065,and 32000027)。
文摘Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the“START”button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.
基金We thank the financial support from National Natural Science Foundation of China(81401252)MerckSerono China Research Fund for Fertility Experts.
文摘Background:To study the effects of cryopreservation on human sperm glycocalyx.Methods:The lectin binding profilings of sperm after freeze-thaw were compared by lectin microarray.Results:CryoSperm^(TM) and direct fumigation were confirmed to be the optimized cryoprotectant and method by comparing the sperm recovery rate.In 91 lectins,33 lectins were significantly changed after sperm cryopreservation.Among them,9 lectins greatly decreased and 24 lectins mainly increased.The binding signals of MAA,PSA,ABA,and AIA were verified by FACS,and the results were consistent with that of lectin microarray.Conclusions:Sperm glycocalyx had significant changes after cryopreservation.The sialic acid,playing an important role in protecting sperm,was greatly lost,which exposed the inner carbohydrates.Thus,the glycocalyx damage due to the cryopreservation might be one of the reasons for low sperm fertility.
