Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Zhou D., Duyvesteyn HME., Chen C-P., Huang C-G., Chen T-H., Shih S-R., Lin Y-C., Cheng C-Y., Cheng S-H., Huang Y-C., Lin T-Y., Ma C., Huo J., Carrique L., Malinauskas T., Ruza R., Shah PNM., Tan TK., Rijal P., Donat R., Godwin K., Buttigieg K., Tree J., Radecke J., Paterson N., Supasa P., Mongkolsapaya J., Screaton G., Carroll M., Jaramillo J., Knight M., James W., Owens R., Naismith J., Townsend A., Fry E., Zhao Y., Ren J., Stuart D., Huang K-Y.
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 (K D of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å 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.