7KKK

SARS-CoV-2 Spike in complex with neutralizing nanobody Nb6

Summary for 7KKK

• Entry DOI: 10.2210/pdb7kkk/pdb
• EMDB information: 22907 22908 22909 22910 22911
• Descriptor: Spike glycoprotein, Synthetic nanobody Nb6, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, nanobody, vhh, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 477015.67

Authors

Schoof, M.S.,Faust, B.F.,Saunders, R.A.,Sangwan, S.,Rezelj, V.,Hoppe, N.,Boone, M.,Billesboelle, C.B.,Puchades, C.,Azumaya, C.M.,Kratochvil, H.T.,Zimanyi, M.,Desphande, I.,Liang, J.,Dickinson, S.,Nguyen, H.C.,Chio, C.M.,Merz, G.E.,Thompson, M.C.,Diwanji, D.,Schaefer, K.,Anand, A.A.,Dobzinski, N.,Zha, B.S.,Simoneau, C.R.,Leon, K.,White, K.M.,Chio, U.S.,Gupta, M.,Jin, M.,Li, F.,Liu, Y.,Zhang, K.,Bulkley, D.,Sun, M.,Smith, A.M.,Rizo, A.N.,Moss, F.,Brilot, A.F.,Pourmal, S.,Trenker, R.,Pospiech, T.,Gupta, S.,Barsi-Rhyne, B.,Belyy, V.,Barile-Hill, A.W.,Nock, S.,Liu, Y.,Krogan, N.J.,Ralston, C.Y.,Swaney, D.L.,Garcia-Sastre, A.,Ott, M.,Vignuzzi, M.,Walter, P.,Manglik, A.,QCRG Structural Biology Consortium (deposition date: 2020-10-27, release date: 2020-11-11, Last modification date: 2024-10-16)

Primary citation

Schoof, M.,Faust, B.,Saunders, R.A.,Sangwan, S.,Rezelj, V.,Hoppe, N.,Boone, M.,Billesbolle, C.B.,Puchades, C.,Azumaya, C.M.,Kratochvil, H.T.,Zimanyi, M.,Deshpande, I.,Liang, J.,Dickinson, S.,Nguyen, H.C.,Chio, C.M.,Merz, G.E.,Thompson, M.C.,Diwanji, D.,Schaefer, K.,Anand, A.A.,Dobzinski, N.,Zha, B.S.,Simoneau, C.R.,Leon, K.,White, K.M.,Chio, U.S.,Gupta, M.,Jin, M.,Li, F.,Liu, Y.,Zhang, K.,Bulkley, D.,Sun, M.,Smith, A.M.,Rizo, A.N.,Moss, F.,Brilot, A.F.,Pourmal, S.,Trenker, R.,Pospiech, T.,Gupta, S.,Barsi-Rhyne, B.,Belyy, V.,Barile-Hill, A.W.,Nock, S.,Liu, Y.,Krogan, N.J.,Ralston, C.Y.,Swaney, D.L.,Garcia-Sastre, A.,Ott, M.,Vignuzzi, M.,QCRG Structural Biology Consortium,Walter, P.,Manglik, A.
An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.
Science, 370:1473-1479, 2020

PubMed Abstract: 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.

PubMed: 33154106
DOI: 10.1126/science.abe3255

Experimental method

ELECTRON MICROSCOPY (3.03 Å)