Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization v1

• DOI: 10.17504/protocols.io.bi35kgq6
• Publication Date: 2020-08-01T01:56:41Z
• Authors: Bei Wang; Daniel Asarnow; Wen-Hsin Lee; Ching-Wen Huang; Bryan Faust; Patricia Miang Lo...; Eve Zi Xian Ngoh; Markus Bohn; David Bulkley; Andrés Pizzorno; Hwee Ching Tan; Chia-Yin Lee; Rabiatul Adawiyah...; Olivier Terrier; Mun Kuen Soh; Frannie Jiuyi Teo; Yvonne Yee Chin Yeap; Yuanyu Hu; Shirley Gek Kheng...; Sebastian Maurer-...; Laurent Renia; Brendon John Hanson; Manuel Rosa-Calat...; Aashish Manglik; Yifan Cheng; Charles S. Craik; Cheng-I Wang
• Keywords: Vero cell; Bivalent (engine)

In vitro antibody selection against pathogens from naïve combinatorial libraries can yield various classes of antigen-specific binders that are distinct those evolved natural infection. Also, rapid neutralizing discovery be made possible by a strategy selects for interfering with pathogen and host interaction. Here we report the antibodies neutralize SARS-CoV-2, virus responsible COVID-19 pandemic, highly diverse human Fab library. Lead 5A6 blocks receptor binding domain (RBD) viral spike to angiotensin converting enzyme 2 (ACE2), neutralizes SARS-CoV-2 infection Vero E6 cells, reduces replication in reconstituted nasal bronchial epithelium models. has high occupancy on surface exerts its neutralization activity via bivalent mode tip two neighbouring RBDs at ACE2 interaction interface, one “up” other “down” position, explaining superior capacity. Furthermore, is insensitive several mutations identified clinical isolates, including D614G mutant become dominant worldwide. Our results suggest could an effective prophylactic therapeutic treatment COVID-19.