Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.

Pinto, Dora; Park, Young-Jun; Beltramello, Martina; Walls, Alexandra C; Tortorici, M Alejandra; Bianchi, Siro; Jaconi, Stefano; Culap, Katja; Zatta, Fabrizia; De Marco, Anna; Peter, Alessia; Guarino, Barbara; Spreafico, Roberto; Cameroni, Elisabetta; Case, James Brett; Chen, Rita E; Havenar-Daughton, Colin; Snell, Gyorgy; Telenti, Amalio; Virgin, Herbert W; Lanzavecchia, Antonio; Diamond, Michael S; Fink, Katja; Veesler, David; Corti, Davide

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that 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 multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with 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 S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.