A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike Glycoprotein

BioRxiv : the Preprint Server for Biology
M. Gordon JoyceKayvon Modjarrad

Abstract

SARS-CoV-2 is a zoonotic virus that has caused a pandemic of severe respiratory disease-COVID-19-within several months of its initial identification. Comparable to the first SARS-CoV, this novel coronavirus's surface Spike (S) glycoprotein mediates cell entry via the human ACE-2 receptor, and, thus, is the principal target for the development of vaccines and immunotherapeutics. Molecular information on the SARS-CoV-2 S glycoprotein remains limited. Here we report the crystal structure of the SARS-CoV-2 S receptor-binding-domain (RBD) at a the highest resolution to date, of 1.95 Å. We identified a set of SARS-reactive monoclonal antibodies with cross-reactivity to SARS-CoV-2 RBD and other betacoronavirus S glycoproteins. One of these antibodies, CR3022, was previously shown to synergize with antibodies that target the ACE-2 binding site on the SARS-CoV RBD and reduce viral escape capacity. We determined the structure of CR3022, in complex with the SARS-CoV-2 RBD, and defined a broadly reactive epitope that is highly conserved across betacoronaviruses. This epitope is inaccessible in the "closed" prefusion S structure, but is accessible in "open" conformations. This first-ever resolution of a human antibody in complex with SARS-C...Continue Reading

Citations

Aug 6, 2020·Nature Structural & Molecular Biology·Matthew McCallumDavid Veesler
Nov 8, 2020·Science·Kevin W NgGeorge Kassiotis
Apr 11, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Saraiya TanmayKonstantinos Poulas
Jun 24, 2021·Journal of Cellular Biochemistry·Abdolreza EsmaeilzadehMajid Ahmadi
Oct 17, 2020·ACS Pharmacology & Translational Science·Dhanusha A Nalawansha, Kusal T G Samarasinghe
Jun 17, 2020·The Journal of Physical Chemistry Letters·Cécilia HognonAntonio Monari

❮ Previous
Next ❯

Methods Mentioned

BETA
size-exclusion chromatography
phage-display
biolayer interferometry
X-ray

Software Mentioned

EM

Related Concepts

Related Feeds

American Thoracic Society: Allergy, Immunology & Inflammation

This feed has been developed in conjunction with the American Thoracic Society for the benefit of its Allergy, Immunology, and Inflammation Assembly. It highlights new and impactful papers on allergy, asthma, genetics, and the pathogenesis of lung diseases.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.