Hejun Liu, N. Wu, M. Yuan, S. Bangaru, J. Torres, T. Caniels, Jelle van Schooten, Xueyong Zhu, C. D. Lee, P. Brouwer, M. J. V. Gils, R. Sanders, A. Ward, I. Wilson
bioRxiv : the preprint server for biology, 2020
Most antibodies isolated from COVID-19 patients are specific to SARS-CoV-2. COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here we determined a crystal structure of COVA1-16 Fab with the SARS-CoV-2 RBD, and a negative-stain EM reconstruction with the spike glycoprotein trimer, to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long CDR H3, and competes with ACE2 binding due to steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with structural and functional rationale for the epitope conservation, provide a blueprint for development of more universal SARS-like coronavirus vaccines and therapies.
Cited by 43 publications.
Field of study: Biology