7LJR

SARS-CoV-2 Spike Protein Trimer bound to DH1043 fab

Summary for 7LJR

• Entry DOI: 10.2210/pdb7ljr/pdb
• EMDB information: 23400
• Descriptor: Spike glycoprotein, Fab DH1043 heavy chain, Fab DH1043 light chain (3 entities in total)
• Functional Keywords: sars-cov-2 spike protein trimer, 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: 5
• Total formula weight: 504155.61

Authors

Gobeil, S.,Acharya, P. (deposition date: 2021-01-30, release date: 2021-03-31, Last modification date: 2024-03-06)

Primary citation

Li, D.,Edwards, R.J.,Manne, K.,Martinez, D.R.,Schafer, A.,Alam, S.M.,Wiehe, K.,Lu, X.,Parks, R.,Sutherland, L.L.,Oguin, T.H.,McDanal, C.,Perez, L.G.,Mansouri, K.,Gobeil, S.M.C.,Janowska, K.,Stalls, V.,Kopp, M.,Cai, F.,Lee, E.,Foulger, A.,Hernandez, G.E.,Sanzone, A.,Tilahun, K.,Jiang, C.,Tse, L.V.,Bock, K.W.,Minai, M.,Nagata, B.M.,Cronin, K.,Gee-Lai, V.,Deyton, M.,Barr, M.,Von Holle, T.,Macintyre, A.N.,Stover, E.,Feldman, J.,Hauser, B.M.,Caradonna, T.M.,Scobey, T.D.,Moody, M.A.,Cain, D.W.,DeMarco, C.T.,Denny, T.N.,Woods, C.W.,Petzold, E.W.,Schmidt, A.G.,Teng, I.T.,Zhou, T.,Kwong, P.D.,Mascola, J.R.,Graham, B.S.,Moore, I.N.,Seder, R.,Andersen, H.,Lewis, M.G.,Montefiori, D.C.,Sempowski, G.D.,Baric, R.S.,Acharya, P.,Haynes, B.F.,Saunders, K.O.
The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates.
Biorxiv, 2021

PubMed Abstract: SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection , while five non-neutralizing NTD antibodies mediated FcγR-independent infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while antibody-enhanced infection does not necessarily herald enhanced infection , increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.

PubMed: 33442694
DOI: 10.1101/2020.12.31.424729

Experimental method

ELECTRON MICROSCOPY (3.66 Å)