• Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra C Walls, M Alejandra Tortorici, Siro Bianchi, Stefano Jaconi, Katja Culap, Fabrizia Zatta, Anna De Marco, Alessia Peter, Barbara Guarino, Roberto Spreafico, Elisabetta Cameroni, James Brett Case, Rita E Chen, Colin Havenar-Daughton, Gyorgy Snell, Amalio Telenti, Herbert W Virgin, Antonio Lanzavecchia, Michael S Diamond, Katja Fink, David Veesler, and Davide Corti.
• Humabs BioMed SA, Vir Biotechnology, Bellinzona, Switzerland.
• Nature. 2020 Jul 1; 583 (7815): 290-295.

AbstractSevere 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.

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