7LX5

The SARS-CoV-2 spike protein receptor binding domain bound to neutralizing nanobodies WNb 2 and WNb 10

7LX5 の概要

• エントリーDOI: 10.2210/pdb7lx5/pdb
• EMDBエントリー: 23566
• 分子名称: Spike glycoprotein, WNb 2, WNb 10 (3 entities in total)
• 機能のキーワード: sars-cov-2, nanobody cocktail, coronavirus spike, neutralizing nanobody, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 179956.32

構造登録者

Pymm, P.,Glukhova, A.,Tham, W.-H. (登録日: 2021-03-03, 公開日: 2021-05-05, 最終更新日: 2024-10-23)

主引用文献

Pymm, P.,Adair, A.,Chan, L.J.,Cooney, J.P.,Mordant, F.L.,Allison, C.C.,Lopez, E.,Haycroft, E.R.,O'Neill, M.T.,Tan, L.L.,Dietrich, M.H.,Drew, D.,Doerflinger, M.,Dengler, M.A.,Scott, N.E.,Wheatley, A.K.,Gherardin, N.A.,Venugopal, H.,Cromer, D.,Davenport, M.P.,Pickering, R.,Godfrey, D.I.,Purcell, D.F.J.,Kent, S.J.,Chung, A.W.,Subbarao, K.,Pellegrini, M.,Glukhova, A.,Tham, W.H.
Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 10-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.

PubMed: 33893175
DOI: 10.1073/pnas.2101918118

実験手法

ELECTRON MICROSCOPY (3.44 Å)