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

Dora Pinto (1) , Young-Jun Park (2) , Martina Beltramello (1) , Alexandra Walls (2) , M. Alejandra Tortorici (3, 2) , Siro Bianchi (1) , Stefano Jaconi (1) , Katja Culap (1) , Fabrizia Zatta (1) , Anna de Marco (1) , Alessia Peter (1) , Barbara Guarino (1) , Roberto Spreafico (4) , Elisabetta Cameroni (1) , James Brett Case (5) , Rita Chen (5) , Colin Havenar-Daughton (4) , Gyorgy Snell (4) , Amalio Telenti (4) , Herbert W Virgin (4) , Antonio Lanzavecchia (6, 1) , Michael Diamond (5) , Katja Fink (1) , David Veesler (2) , Davide Corti (1)

1 Humabs BioMed SA
2 Department of Biochemistry [Washington ]
3 Virologie Structurale - Structural Virology
4 Vir Biotechnology Inc [San Francisco]
5 Washington University School of Medicine in St. Louis
6 Scuola Universitaria Professionale della Svizzera italiana

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.

Domains: Life Sciences [q-bio]

Dora Pinto, Young-Jun Park, Martina Beltramello, Alexandra Walls, M. Alejandra Tortorici, et al.. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature, 2020, ⟨10.1038/s41586-020-2349-y⟩. ⟨pasteur-02623374⟩