SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2 interface

• DOI: 10.1101/2020.06.05.135921
• Publication Date: 2020-06-06T09:45:11Z
• Authors: Federico Bertoglio; Doris Meier; Nora Langreder; Stephan Steinke; Ulfert Rand; Luca Simonelli; Philip Alexander ...; Rico Ballmann; Kai-Thomas Schneider; Kristian Daniel R...; Maximilian Ruschig; Peggy Riese; Kathrin Eschke; Yeonsu Kim; Dorina Schäckermann; Mattia Pedotti; Philipp Kuhn; Susanne Zock-Emme...; Johannes Wöhrle; Normann Kilb; Tobias Herz; Marlies Becker; Martina Grasshoff; Esther Veronika W...; Giulio Russo; Andrea Kröger; Linda Brunotte; Stephan Ludwig; Viola Fühner; Stefan Daniel Krämer; Stefan Dübel; Luca Varani; Günter Roth; Luka Čičin-Šain; Maren Schubert; Michael Hust
• Keywords: Vero cell; Coronavirus

Abstract COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, novel betacoronavirus discovered in December 2019 and closely related to the SARS coronavirus (CoV). Both viruses use human ACE2 receptor for cell entry, recognizing it with Receptor Binding Domain (RBD) of S1 subunit viral spike (S) protein. The S2 domain mediates fusion host membrane. Experience MERS coronaviruses has shown that potent monoclonal neutralizing antibodies against RBD can inhibit interaction virus cellular (ACE2 SARS) block entry. Assuming similar strategy would be successful we used phage display select from naïve universal antibody gene libraries HAL9/10 anti-SARS-CoV-2 capable inhibiting ACE2. 309 unique fully were identified. 17 showed more than 75% inhibition binding cells expressing scFv-Fc format, assessed flow cytometry several even an 50% at molar ratio protein or 1:1. All able bind isolated RBD, four them sub-nanomolar EC50. Furthermore, these neutralized active SARS-CoV-2 infection VeroE6 cells. In final step, best as converted into IgG format. STE73-2E9 neutralization IC50 0.43 nM ACE2-RBD interface. Universal healthy donors offer advantage generated quickly independent availability material recovered patients pandemic situation.