Dear Editor,COVID-19 lung pathology is characterized by interstitial pneumonia with cell-cell fusion-induced syncytia and extensive tissue damage.1 The correlation between viral fusogenicity and pathogenicity has been...Dear Editor,COVID-19 lung pathology is characterized by interstitial pneumonia with cell-cell fusion-induced syncytia and extensive tissue damage.1 The correlation between viral fusogenicity and pathogenicity has been reported in SARS-CoV-2 variants.2 Compared with the previous Delta or D614G variants,Omicron BA.1 has been proven to be less fusogenic and pathogenic.展开更多
Neutralizing antibodies have been proven to be highly effective in treating mild and moderate COVID-19 patients,but continuous emergence of SARS-CoV-2 variants poses significant challenges.Antibody cocktail treatments...Neutralizing antibodies have been proven to be highly effective in treating mild and moderate COVID-19 patients,but continuous emergence of SARS-CoV-2 variants poses significant challenges.Antibody cocktail treatments reduce the risk of escape mutants and resistance.In this study,a new cocktail composed of two highly potent neutralizing antibodies(HB27 and H89Y)was developed,whose binding epitope is different from those cocktails that received emergency use authorization.This cocktail showed more potent and balanced neutralizing activities(IC_(50)0.9–11.3 ng mL^(-1))against a broad spectrum of SARS-CoV-2 variants over individual HB27 or H89Y antibodies.Furthermore,the cocktail conferred more effective protection against the SARS-CoV-2 Beta variant in an aged murine model than monotherapy.It was shown to prevent SARS-CoV-2 mutational escape in vitro and effectively neutralize 61 types of pseudoviruses harbouring single amino acid mutation originated from variants and escape strains of Bamlanivimab,Casirivimab and Imdevimab with IC_(50)of 0.6–65 ng mL^(-1).Despite its breadth of variant neutralization,the HB27+H89Y combo and EUA cocktails lost their potencies against Omicron variant.Our results provide important insights that new antibody cocktails covering different epitopes are valuable tools to counter virus mutation and escape,highlighting the need to search for more conserved epitopes to combat Omicron.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
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting ...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting in more than 1 million deaths globally.It is well recognized that SARSCoV-2 preferentially attacks pulmonary epithelial cells,leading to acute respiratory distress syndrome(ARDS).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Beijing Municipal Science and Technology Commission(Z211100002521026).
文摘Dear Editor,COVID-19 lung pathology is characterized by interstitial pneumonia with cell-cell fusion-induced syncytia and extensive tissue damage.1 The correlation between viral fusogenicity and pathogenicity has been reported in SARS-CoV-2 variants.2 Compared with the previous Delta or D614G variants,Omicron BA.1 has been proven to be less fusogenic and pathogenic.
基金supported by the National Key Research and Development Project of China(2021YEF0201700)。
文摘Neutralizing antibodies have been proven to be highly effective in treating mild and moderate COVID-19 patients,but continuous emergence of SARS-CoV-2 variants poses significant challenges.Antibody cocktail treatments reduce the risk of escape mutants and resistance.In this study,a new cocktail composed of two highly potent neutralizing antibodies(HB27 and H89Y)was developed,whose binding epitope is different from those cocktails that received emergency use authorization.This cocktail showed more potent and balanced neutralizing activities(IC_(50)0.9–11.3 ng mL^(-1))against a broad spectrum of SARS-CoV-2 variants over individual HB27 or H89Y antibodies.Furthermore,the cocktail conferred more effective protection against the SARS-CoV-2 Beta variant in an aged murine model than monotherapy.It was shown to prevent SARS-CoV-2 mutational escape in vitro and effectively neutralize 61 types of pseudoviruses harbouring single amino acid mutation originated from variants and escape strains of Bamlanivimab,Casirivimab and Imdevimab with IC_(50)of 0.6–65 ng mL^(-1).Despite its breadth of variant neutralization,the HB27+H89Y combo and EUA cocktails lost their potencies against Omicron variant.Our results provide important insights that new antibody cocktails covering different epitopes are valuable tools to counter virus mutation and escape,highlighting the need to search for more conserved epitopes to combat Omicron.
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 Ministry of Science and Technology of the People’s Republic of China(2020YFC0844900,2020YFC0841700,and 2020YFC0848700)the National Natural Science Foundation of China(81470566,81670765,81772165,and 81974303)+1 种基金the China Primary Health Care Foundation-Youan Medical Development Fund(BJYAYY2020PY-01)the funds from Neoline,Gbio and Quanterix。
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused the global outbreak of coronavirus disease 2019(COVID-19).By far,more than 35 million people had been infected by SARS-CoV-2,resulting in more than 1 million deaths globally.It is well recognized that SARSCoV-2 preferentially attacks pulmonary epithelial cells,leading to acute respiratory distress syndrome(ARDS).
基金This work was 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.
