6WS6

Structural and functional analysis of a potent sarbecovirus neutralizing antibody

Summary for 6WS6

• Entry DOI: 10.2210/pdb6ws6/pdb
• Descriptor: S309 antigen-binding (Fab) fragment, heavy chain, S309 antigen-binding (Fab) fragment, light chain, O-(O-(2-AMINOPROPYL)-O'-(2-METHOXYETHYL)POLYPROPYLENE GLYCOL 500) (3 entities in total)
• Functional Keywords: fusion protein, neutralizing antibody, sarbecovirus, structural genomics, seattle structural genomics center for infectious disease, ssgcid, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 143932.33

Authors

Pinto, D.,Park, Y.J.,Beltramello, M.,Walls, A.C.,Tortorici, M.A.,Bianchi, S.,Jaconi, S.,Culap, K.,Zatta, F.,Marco, A.D.,Peter, A.,Guarino, B.,Spreafico, R.,Cameroni, E.,Case, J.B.,Chen, R.E.,Havenar-Daughton, C.,Snell, G.,Telenti, A.,Virgin, H.W.,Lanzavecchia, A.,Diamond, M.S.,Fink, K.,Veesler, D.,Corti, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2020-04-30, release date: 2020-05-27, Last modification date: 2024-10-23)

Primary citation

Pinto, D.,Park, Y.J.,Beltramello, M.,Walls, A.C.,Tortorici, M.A.,Bianchi, S.,Jaconi, S.,Culap, K.,Zatta, F.,De Marco, A.,Peter, A.,Guarino, B.,Spreafico, R.,Cameroni, E.,Case, J.B.,Chen, R.E.,Havenar-Daughton, C.,Snell, G.,Telenti, A.,Virgin, H.W.,Lanzavecchia, A.,Diamond, M.S.,Fink, K.,Veesler, D.,Corti, D.
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Nature, 583:290-295, 2020

PubMed 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 2020. 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.

PubMed: 32422645
DOI: 10.1038/s41586-020-2349-y

Experimental method

X-RAY DIFFRACTION (3.3 Å)