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

Zhou, Daming; Duyvesteyn, Helen M E; 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 N M; Tan, Tiong Kit; Rijal, Pramila; Donat, Robert F; Godwin, Kerry; Buttigieg, Karen R; Tree, Julia A; Radecke, Julika; Paterson, Neil G; Supasa, Piyada; Mongkolsapaya, Juthathip; Screaton, Gavin R; Carroll, Miles W; Gilbert-Jaramillo, Javier; Knight, Michael L; James, William; Owens, Raymond J; Naismith, James H; Townsend, Alain R; Fry, Elizabeth E; Zhao, Yuguang; Ren, Jingshan; Stuart, David I; Huang, Kuan-Ying A

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