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

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.

SUBMITTER: Liu H 

PROVIDER: S-EPMC7418720 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Liu Hejun H   Wu Nicholas C NC   Yuan Meng M   Bangaru Sandhya S   Torres Jonathan L JL   Caniels Tom G TG   van Schooten Jelle J   Zhu Xueyong X   Lee Chang-Chun D CD   Brouwer Philip J M PJM   van Gils Marit J MJ   Sanders Rogier W RW   Ward Andrew B AB   Wilson Ian A IA  

bioRxiv : the preprint server for biology 20200803

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  ...[more]

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