Details

Autor(en) / Beteiligte

• Huo, Jiandong
• Zhao, Yuguang
• Ren, Jingshan
• Zhou, Daming
• Duyvesteyn, Helen M.E.
• Ginn, Helen M.
• Carrique, Loic
• Malinauskas, Tomas
• Ruza, Reinis R.
• Shah, Pranav N.M.
• Tan, Tiong Kit
• Rijal, Pramila
• Coombes, Naomi
• Bewley, Kevin R.
• Tree, Julia A.
• Radecke, Julika
• Paterson, Neil G.
• Supasa, Piyada
• Mongkolsapaya, Juthathip
• Screaton, Gavin R.
• Carroll, Miles
• Townsend, Alain
• Fry, Elizabeth E.
• Owens, Raymond J.
• Stuart, David I.

Titel

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike

Ist Teil von

• Cell host & microbe, 2020-09, Vol.28 (3), p.445-454.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •CR3022 binds the RBD of SARS-CoV-2 and shows strong neutralization•Neutralization is by destroying the prefusion spike conformation•CR3022 binds a highly conserved epitope that is inaccessible in prefusion spike protein•CR3022 could have therapeutic potential alone or in synergy with a receptor blocker Huo et al. find that the antibody CR3022 binds tightly to the receptor binding domain of the SARS-CoV-2 spike at a site different to that used by the receptor. CR3022 effectively neutralizes the virus, and cryo-EM reveals that it disrupts the spike. Such antibodies could have potential as COVID-19 therapeutics.