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bioRxiv · 10.1101/2020.08.02.233536

Cross-neutralization of a SARS-CoV-2 antibody to a functionally conserved site is mediated by avidity

Liu, H.·Wu, N. C.·Yuan, M.·Bangaru, S.·Torres, J. L.·Caniels, T. G.·van Schooten, J.·Zhu, X.·Lee, C.-C. D.·Brouwer, P. J. M.·van Gils, M. J.·Sanders, R. W.·Ward, A. B.·Wilson, I. A.
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Abstract

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.

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Liu, H., Wu, N. C., Yuan, M., Bangaru, S., Torres, J. L., Caniels, T. G., van Schooten, J., Zhu, X., Lee, C.-C. D., Brouwer, P. J. M., van Gils, M. J., Sanders, R. W., Ward, A. B., Wilson, I. A.. 2020-08-03. Cross-neutralization of a SARS-CoV-2 antibody to a functionally conserved site is mediated by avidity. https://doi.org/10.1101/2020.08.02.233536

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