In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a ...In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.展开更多
Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http:/...Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http://www.who.int/emergencies/mers-cov/en/). MERS-CoV causes an acute and severe respiratory illness with a high mortality rate(~35%) in humans (Shi et al., 2017, Zaki et al., 2012).Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease (Agrawal et al., 2016, Ying et al., 2014).展开更多
The novel coronavirus SARS-CoV-2 has infected more than 104 million individuals and resulted in more than 2.2 million deaths worldwide as of February 7,2021(https://covid19.who.int).The COVID-19 pandemic highlights th...The novel coronavirus SARS-CoV-2 has infected more than 104 million individuals and resulted in more than 2.2 million deaths worldwide as of February 7,2021(https://covid19.who.int).The COVID-19 pandemic highlights the need for safe and effective vaccines against SARS-CoV-2 infection.展开更多
Since severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019(COVID-19),th...Since severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019(COVID-19),this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses.A total of 120 CD8^(+)T cell epitopes from the E,M,N,S,and RdRp proteins were functionally validated.Among these,110,15,6,14,and 12 epitopes were highly homologous with SARS-CoV,OC43,NL63,HKU1,and 229E,respectively;in addition,four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants.Then,31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C),R848 or poly(lactic-co-glycolic acid)nanoparticles,and these vaccines elicited robust and specific CD8^(+)T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice.In contrast to previous research,this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes,provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations,and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype,which initially confirmed the in vivo feasibility of 9-or 10-mer peptide cocktail vaccines against SARS-CoV-2.These data will facilitate the design and development of vaccines that induce antiviral CD8^(+)T cell responses in COVID-19 patients.展开更多
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a ...In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.展开更多
基金supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)Young Talent fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.
基金supported by the National Key Research and Development Program of China (2016YFD0500300 to Wenjie Tan)
文摘Dear Editor,Since September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) cases have been reported in more than 27 countries, and more than 2,000 cases have been confirmed in the laboratory (http://www.who.int/emergencies/mers-cov/en/). MERS-CoV causes an acute and severe respiratory illness with a high mortality rate(~35%) in humans (Shi et al., 2017, Zaki et al., 2012).Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease (Agrawal et al., 2016, Ying et al., 2014).
基金supported by the National Key Plan for Scientific Research and Development of China(2020YFC0860100,2020YFC0841401,2016YFD0500306)the National Natural Science Foundation of China(82041006)the National Science and Technology Major Project of China(No.2017ZX10304402003001).
文摘The novel coronavirus SARS-CoV-2 has infected more than 104 million individuals and resulted in more than 2.2 million deaths worldwide as of February 7,2021(https://covid19.who.int).The COVID-19 pandemic highlights the need for safe and effective vaccines against SARS-CoV-2 infection.
基金This work was supported by the National Nature Science Foundation of China(82041006)the COVID-19 Emergency Research Fund of Zhejiang University of China(2020XGZX021).
文摘Since severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)-specific T cells have been found to play essential roles in host immune protection and pathology in patients with coronavirus disease 2019(COVID-19),this study focused on the functional validation of T cell epitopes and the development of vaccines that induce specific T cell responses.A total of 120 CD8^(+)T cell epitopes from the E,M,N,S,and RdRp proteins were functionally validated.Among these,110,15,6,14,and 12 epitopes were highly homologous with SARS-CoV,OC43,NL63,HKU1,and 229E,respectively;in addition,four epitopes from the S protein displayed one amino acid that was distinct from the current SARS-CoV-2 variants.Then,31 epitopes restricted by the HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C),R848 or poly(lactic-co-glycolic acid)nanoparticles,and these vaccines elicited robust and specific CD8^(+)T cell responses in HLA-A2/DR1 transgenic mice as well as wild-type mice.In contrast to previous research,this study established a modified DC-peptide-PBL cell coculture system using healthy donor PBMCs to validate the in silico predicted epitopes,provided an epitope library restricted by nine of the most prevalent HLA-A allotypes covering broad Asian populations,and identified the HLA-A restrictions of these validated epitopes using competitive peptide binding experiments with HMy2.CIR cell lines expressing the indicated HLA-A allotype,which initially confirmed the in vivo feasibility of 9-or 10-mer peptide cocktail vaccines against SARS-CoV-2.These data will facilitate the design and development of vaccines that induce antiviral CD8^(+)T cell responses in COVID-19 patients.
基金supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)Young Talent fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.
