• Jiandong Huo, Yuguang Zhao, Jingshan Ren, Daming Zhou, Helen M E Duyvesteyn, Helen M Ginn, Loic Carrique, Tomas Malinauskas, Reinis R Ruza, Pranav N M Shah, Tiong Kit Tan, Pramila Rijal, Naomi Coombes, Kevin R Bewley, Julia A Tree, Julika Radecke, Neil G Paterson, Piyada Supasa, Juthathip Mongkolsapaya, Gavin R Screaton, Miles Carroll, Alain Townsend, Elizabeth E Fry, Raymond J Owens, and David I Stuart.
• Division of Structural Biology, University of Oxford, The Wellcome Centre for Human Genetics, Headington, Oxford, OX3 7BN, UK; The Rosalind Franklin Institute, Harwell Campus, OX11 0FA, UK; Protein Production UK, Research Complex at Harwell, Harwell Science & Innovation Campus, Didcot, OX11 0FA, UK.
• Cell Host Microbe. 2020 Sep 9; 28 (3): 445-454.e6.

AbstractThere 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.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

62 keywords...

hide…