The authors have retracted this article [1]. After the publication ofthis article, it came to the authors attention that in order tosupport the conclusions of the study, the authors should haveused primary T cells ins...The authors have retracted this article [1]. After the publication ofthis article, it came to the authors attention that in order tosupport the conclusions of the study, the authors should haveused primary T cells instead of T cell lines. Additionally, there areconcerns that the flow cytometry methodology applied here wasflawed. These points resulted in the conclusions being consideredinvalid.展开更多
The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed serious threats to global health and economy,thus calling for the development of safe an...The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed serious threats to global health and economy,thus calling for the development of safe and effective vaccines.The receptorbinding domain(RBD)in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2(ACE2)receptor.It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines.Here,we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG,as an immunopotentiator,elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections.The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus(SARSr-CoV).Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge.These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants,as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.展开更多
The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SAR...The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,as well as future outbreaks of emerging CoVs.We have previously identified a polyethylene glycol-conjugated(PEGylated)lipopeptide,EK1C4,with potent pan-CoV fusion inhibitory activity.However,PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo.Therefore,we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment(HR2-CF)of HCoV-OC43.Among these lipopeptides,EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike(S)mutants,as well as other HCoVs and some bat SARS-related coronaviruses(SARSr-CoVs)tested.The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes,better metabolic stability in mouse serum,higher thermostability than the PEGylated lipopeptide EK1C4,suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.展开更多
Dear Editor,The rapid spread of SARS-CoV-2(also known as 2019-nCoV and HCoV-191),a novel lineage B betacoronavirus(βCoV),has caused a global pandemic of coronavirus disease(COVID-19).It has been speculated that RRAR,...Dear Editor,The rapid spread of SARS-CoV-2(also known as 2019-nCoV and HCoV-191),a novel lineage B betacoronavirus(βCoV),has caused a global pandemic of coronavirus disease(COVID-19).It has been speculated that RRAR,a unique furin-like cleavage site(FCS)in the spike protein(S),which is absent in other lineage BβCoVs,such as SARS-CoV,is responsible for its high infectivity and transmissibility.展开更多
The authors have retracted this article1.After the publication of this article,it came to the authors attention that in order to support the conclusions of the study,the authors should have used primary T cells instea...The authors have retracted this article1.After the publication of this article,it came to the authors attention that in order to support the conclusions of the study,the authors should have used primary T cells instead of T-cell lines.In addition,there are concerns that the flow cytometry methodology applied here was flawed.These points resulted in the conclusions being considered invalid.展开更多
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design.Here,we identified a receptorbind...New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design.Here,we identified a receptorbinding domain(RBD)-binding antibody,XG014,which potently neutralizesβ-coronavirus lineage B(β-CoV-B),including SARS-CoV-2,its circulating variants,SARSCoV and bat SARSr-CoV WIV1.Interestingly,antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibodydependent SARS-CoV-2 spike(S)protein-mediated cellcell fusion,suggesting a unique mode of recognition by XG014.Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional“down”conformation,while its family member XG005 directly competes with ACE2 binding and position the RBD“up”.Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo.Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines againstβ-CoV-B and newly emerging SARS-CoV-2 variants of concern.展开更多
Dear Editor,An outbreak of unusual pneumonia in Wuhan, China recently was caused by infection of a novel type of coronavirus. The virus and disease were denoted as 2019-nCoV and COVID-19, respectively, by the World He...Dear Editor,An outbreak of unusual pneumonia in Wuhan, China recently was caused by infection of a novel type of coronavirus. The virus and disease were denoted as 2019-nCoV and COVID-19, respectively, by the World Health Organization(WHO). Most recently, 2019-nCoV was renamed SARS-CoV-2 by Coronaviridae Study Group(CSG) of the International Committee on Taxonomy of Viruses(ICTV)(Gorbalenya et al. 2020)。展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants have caused>5oo million confirmed cases and>6 million deaths.Apart from the common clinical manifestations,63% of admitted coronavirus ...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants have caused>5oo million confirmed cases and>6 million deaths.Apart from the common clinical manifestations,63% of admitted coronavirus disease 2019(COvID-19)patients had lymphopenia,increasingto 85% in patients with severe disease(Huang et al.,2020).展开更多
Dear Editor,Fan et al.have shown that whey protein,such as that found in human,bovine,and goat milk,could effectively inhibit SARS-CoV-2 infection,but they did not identify the components in whey protein having this a...Dear Editor,Fan et al.have shown that whey protein,such as that found in human,bovine,and goat milk,could effectively inhibit SARS-CoV-2 infection,but they did not identify the components in whey protein having this activity.1 Since p-lactoglobulin(P-LG)is the main component of whey protein,we herein tested the anti-SARS-CoV-2 activity of p-LG and 3-hydroxyphthalic anhydride(3HP)-modified P-LG(3HP-P-LG),an active component in anti-human papillomavirus(HPV)biological dressing(JB01-BD)that has been used in clinics since 2013 to block cervical infection of HPV.展开更多
文摘The authors have retracted this article [1]. After the publication ofthis article, it came to the authors attention that in order tosupport the conclusions of the study, the authors should haveused primary T cells instead of T cell lines. Additionally, there areconcerns that the flow cytometry methodology applied here wasflawed. These points resulted in the conclusions being consideredinvalid.
基金supported by grants from National Natural Science Foundation of China(82041025 to S.J.,81822045 to L.L.)Development Programs for COVID-19 of Shanghai Science and Technology Commission(Grant No.20431900401).
文摘The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed serious threats to global health and economy,thus calling for the development of safe and effective vaccines.The receptorbinding domain(RBD)in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2(ACE2)receptor.It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines.Here,we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG,as an immunopotentiator,elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections.The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus(SARSr-CoV).Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge.These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants,as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.
基金This work was supported by the National Natural Science Foundation of China(81822045 and 82041036 to Lu Lu,82041025 to Shibo Jiang,21877127 to Chao Wang)the Program of Shanghai Academic/Technology Research Leader(20XD1420300 to Lu Lu,China).
文摘The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,as well as future outbreaks of emerging CoVs.We have previously identified a polyethylene glycol-conjugated(PEGylated)lipopeptide,EK1C4,with potent pan-CoV fusion inhibitory activity.However,PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo.Therefore,we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment(HR2-CF)of HCoV-OC43.Among these lipopeptides,EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike(S)mutants,as well as other HCoVs and some bat SARS-related coronaviruses(SARSr-CoVs)tested.The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes,better metabolic stability in mouse serum,higher thermostability than the PEGylated lipopeptide EK1C4,suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.
基金funded by the National Megaprojects of China for Major Infectious Diseases(2018ZX10301403)The National Natural Science Foundation of China(81822045 to L.L.+1 种基金81630090 to S.J.,81701998 to Q.W.,and 81703571 to W.X.)the China Postdoctoral Science Foundation(2018M640341,2019T120302 to S.X.).
文摘Dear Editor,The rapid spread of SARS-CoV-2(also known as 2019-nCoV and HCoV-191),a novel lineage B betacoronavirus(βCoV),has caused a global pandemic of coronavirus disease(COVID-19).It has been speculated that RRAR,a unique furin-like cleavage site(FCS)in the spike protein(S),which is absent in other lineage BβCoVs,such as SARS-CoV,is responsible for its high infectivity and transmissibility.
文摘The authors have retracted this article1.After the publication of this article,it came to the authors attention that in order to support the conclusions of the study,the authors should have used primary T cells instead of T-cell lines.In addition,there are concerns that the flow cytometry methodology applied here was flawed.These points resulted in the conclusions being considered invalid.
基金the National Natural Science Foundation of China(81822045 and 82041036 to L.L.,81900729 to L.S.,31872730 and 32070947 to Q.W.)the Program of Shanghai Academic/Technology Research Leader(20XD1420300 to L.L.).
文摘New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design.Here,we identified a receptorbinding domain(RBD)-binding antibody,XG014,which potently neutralizesβ-coronavirus lineage B(β-CoV-B),including SARS-CoV-2,its circulating variants,SARSCoV and bat SARSr-CoV WIV1.Interestingly,antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibodydependent SARS-CoV-2 spike(S)protein-mediated cellcell fusion,suggesting a unique mode of recognition by XG014.Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional“down”conformation,while its family member XG005 directly competes with ACE2 binding and position the RBD“up”.Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo.Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines againstβ-CoV-B and newly emerging SARS-CoV-2 variants of concern.
基金supported by the National Megaprojects of China for Major Infectious Diseases (2018ZX10301403)。
文摘Dear Editor,An outbreak of unusual pneumonia in Wuhan, China recently was caused by infection of a novel type of coronavirus. The virus and disease were denoted as 2019-nCoV and COVID-19, respectively, by the World Health Organization(WHO). Most recently, 2019-nCoV was renamed SARS-CoV-2 by Coronaviridae Study Group(CSG) of the International Committee on Taxonomy of Viruses(ICTV)(Gorbalenya et al. 2020)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants have caused>5oo million confirmed cases and>6 million deaths.Apart from the common clinical manifestations,63% of admitted coronavirus disease 2019(COvID-19)patients had lymphopenia,increasingto 85% in patients with severe disease(Huang et al.,2020).
基金This study was funded by the National Natural Science Foundation of China(Grant No.82161138002 to SJ)the Natural Science Foundation of Guangdong Province(2018B030312010 to S.L.)the Science Research Project of the Foshan City(2020001000206 to Z.Y.).
文摘Dear Editor,Fan et al.have shown that whey protein,such as that found in human,bovine,and goat milk,could effectively inhibit SARS-CoV-2 infection,but they did not identify the components in whey protein having this activity.1 Since p-lactoglobulin(P-LG)is the main component of whey protein,we herein tested the anti-SARS-CoV-2 activity of p-LG and 3-hydroxyphthalic anhydride(3HP)-modified P-LG(3HP-P-LG),an active component in anti-human papillomavirus(HPV)biological dressing(JB01-BD)that has been used in clinics since 2013 to block cervical infection of HPV.