Structural and functional analysis of a potent sarbecovirus neutralizing antibody

• DOI: 10.1101/2020.04.07.023903
• Publication Date: 2020-04-09T14:00:51Z
• Authors: Dora Pinto; Young-Jun Park; Martina Beltramello; Alexandra C. Walls; M. Alejandra Tort...; 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-Dau...; Gyorgy Snell; Amalio Telenti; Herbert W. Virgin; Antonio Lanzavecchia; Michael S. Diamond; Katja Fink; David Veesler; Davide Corti
• Keywords: Pandemic; Coronavirus

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths 1,2 . Vaccine therapeutic discovery efforts are paramount to curb spread of this zoonotic virus. The spike (S) glycoprotein promotes entry into host cells main target neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting S identified from memory B SARS survivor infected 2003. One antibody, named S309, potently neutralizes SARS-CoV pseudoviruses as well authentic by engaging receptor-binding domain. Using cryo-electron microscopy binding assays, show S309 recognizes glycan-containing epitope conserved within sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including along other here further enhanced neutralization may limit emergence neutralization-escape mutants. These results pave way using S309-containing antibody prophylaxis individuals at high risk exposure or post-exposure therapy treat severe disease.