Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.

Original publication

DOI

10.1016/j.chom.2020.06.010

Type

Journal article

Journal

Cell Host Microbe

Publication Date

09/09/2020

Volume

28

Pages

445 - 454.e6

Keywords

CR3022, SARS-CoV-2, X-ray crystallography, antibody, cryo-electron microscopy, epitope, neutralization, receptor binding domain, spike, therapeutic, Allosteric Site, Amino Acid Sequence, Angiotensin-Converting Enzyme 2, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antigen-Antibody Complex, Betacoronavirus, COVID-19, COVID-19 Vaccines, Coronavirus Infections, Cryoelectron Microscopy, Crystallography, X-Ray, Host Microbial Interactions, Humans, Models, Molecular, Neutralization Tests, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Receptors, Virus, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Viral Vaccines, Virus Internalization