7LAA

Structure of SARS-CoV-2 S protein in complex with Receptor Binding Domain antibody DH1041

Summary for 7LAA

• Entry DOI: 10.2210/pdb7laa/pdb
• Related: 7LAB 7LCN 7LD1
• EMDB information: 23246
• Descriptor: Spike glycoprotein, DH1041 heavy chain, DH1041 light chain, ... (6 entities in total)
• Functional Keywords: rbd antibody, dh1041, sars, covid-19, sars-cov-2 2p s ectodomain, viral protein, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 5
• Total formula weight: 431493.97

Authors

Manne, K.,Acharya, P. (deposition date: 2021-01-06, release date: 2021-03-17, Last modification date: 2021-08-18)

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 3rd, 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.,Rountree, W.,Wang, Y.,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.
In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.
Cell, 184:4203-, 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) or 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 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 in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 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 in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.

PubMed: 34242577
DOI: 10.1016/j.cell.2021.06.021

Experimental method

ELECTRON MICROSCOPY (3.42 Å)