Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Zhou, Daming; Duyvesteyn, Helen ME; Chen, Cheng-Pin; Huang, Chung-Guei; Chen, Ting-Hua; Shih, Shin-Ru; Lin, Yi-Chun; Cheng, Chien-Yu; Cheng, Shu-Hsing; Huang, Yhu-Chering; Lin, Tzou-Yien; Ma, Che; Huo, Jiandong; Carrique, Loic; Malinauskas, Tomas; Ruza, Reinis R; Shah, Pranav NM; Tan, Tiong Kit; Rijal, Pramila; Donat, Robert F.; Godwin, Kerry; Buttigieg, Karen; Tree, Julia; Radecke, Julika; Paterson, Neil G; Supasa, Piyasa; Mongkolsapaya, Juthathip; Screaton, Gavin R; Carroll, Miles W.; Jaramillo, Javier G.; Knight, Michael; James, William; Owens, Raymond J; Naismith, James H.; Townsend, Alain; Fry, Elizabeth E; Zhao, Yuguang; Ren, Jingshan; Stuart, David I; Huang, Kuan-Ying A.

The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Ã… crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19.