EMD-21865
Structure of the SARS-CoV-2 spike glycoprotein in complex with the S309 neutralizing antibody Fab fragment (open state)
EMD-21865
Single-particle3.7 Å
Deposition: 27/04/2020Map released: 27/05/2020
Last modified: 16/10/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 spike glycoprotein ectodomain in complex with the S309 neutralizing antibody Fab fragment (open state)
Fitted models: 6wpt (Avg. Q-score: 0.393)
Deposition Authors: Pinto D, Park YJ
Sample: SARS-CoV-2 spike glycoprotein ectodomain in complex with the S309 neutralizing antibody Fab fragment (open state)
Fitted models: 6wpt (Avg. Q-score: 0.393)
Deposition Authors: Pinto D, Park YJ
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Pinto D,
Park YJ ,
Beltramello M,
Walls AC ,
Tortorici MA ,
Bianchi S ,
Jaconi S,
Culap K ,
Zatta F ,
De Marco A,
Peter A,
Guarino B ,
Spreafico R ,
Cameroni E,
Case JB ,
Chen RE,
Havenar-Daughton C ,
Snell G,
Telenti A,
Virgin HW ,
Lanzavecchia A,
Diamond MS,
Fink K,
Veesler D ,
Corti D
(2020) Nature , 583 , 290 - 295
,
Beltramello M,
Walls AC ,
Tortorici MA ,
Bianchi S ,
Jaconi S,
Culap K ,
Zatta F ,
De Marco A,
Peter A,
Guarino B ,
Spreafico R ,
Cameroni E,
Case JB ,
Chen RE,
Havenar-Daughton C ,
Snell G,
Telenti A,
Virgin HW ,
Lanzavecchia A,
Diamond MS,
Fink K,
Veesler D ,
Corti D
(2020) Nature , 583 , 290 - 295
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.