Details

Autor(en) / Beteiligte

• Schoof, Michael
• Faust, Bryan
• Saunders, Reuben A
• Sangwan, Smriti
• Rezelj, Veronica
• Hoppe, Nick
• Boone, Morgane
• Billesbølle, Christian B
• Puchades, Cristina
• Azumaya, Caleigh M
• Kratochvil, Huong T
• Zimanyi, Marcell
• Deshpande, Ishan
• Liang, Jiahao
• Dickinson, Sasha
• Nguyen, Henry C
• Chio, Cynthia M
• Merz, Gregory E
• Thompson, Michael C
• Diwanji, Devan
• Schaefer, Kaitlin
• Anand, Aditya A
• Dobzinski, Niv
• Zha, Beth Shoshana
• Simoneau, Camille R
• Leon, Kristoffer
• White, Kris M
• Chio, Un Seng
• Gupta, Meghna
• Jin, Mingliang
• Li, Fei
• Liu, Yanxin
• Zhang, Kaihua
• Bulkley, David
• Sun, Ming
• Smith, Amber M
• Rizo, Alexandrea N
• Moss, Frank
• Brilot, Axel F
• Pourmal, Sergei
• Trenker, Raphael
• Pospiech, Thomas
• Gupta, Sayan
• Barsi-Rhyne, Benjamin
• Belyy, Vladislav
• Barile-Hill, Andrew W
• Nock, Silke
• Liu, Yuwei
• Krogan, Nevan J
• Ralston, Corie Y
• Swaney, Danielle L
• García-Sastre, Adolfo
• Ott, Melanie
• Vignuzzi, Marco
• Walter, Peter
• Manglik, Aashish

Titel

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike

Ist Teil von

• Science (American Association for the Advancement of Science), 2020-12, Vol.370 (6523), p.1473-1479

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.