ジャーナル: Cell Host Microbe / 年: 2020 タイトル: Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike. 著者: 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 ...著者: 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 / David I Stuart / 要旨: 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 ...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.