7SG4

Structure of SARS-CoV S protein in complex with Receptor Binding Domain antibody DH1047

Summary for 7SG4

• Entry DOI: 10.2210/pdb7sg4/pdb
• Related: 7LD1
• EMDB information: 23279 25105
• Descriptor: Spike glycoprotein, DH1047 Heavy chain, DH1047 light chain, ... (4 entities in total)
• Functional Keywords: sars-cov spike protein trimer, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus (SARS-CoV); More
• Total number of polymer chains: 5
• Total formula weight: 481563.10

Authors

Gobeil, S.,Acharya, P. (deposition date: 2021-10-04, release date: 2021-11-10, Last modification date: 2024-10-23)

Primary citation

Martinez, D.R.,Schafer, A.,Gobeil, S.,Li, D.,De la Cruz, G.,Parks, R.,Lu, X.,Barr, M.,Stalls, V.,Janowska, K.,Beaudoin, E.,Manne, K.,Mansouri, K.,Edwards, R.J.,Cronin, K.,Yount, B.,Anasti, K.,Montgomery, S.A.,Tang, J.,Golding, H.,Shen, S.,Zhou, T.,Kwong, P.D.,Graham, B.S.,Mascola, J.R.,Montefiori, D.C.,Alam, S.M.,Sempowski, G.,Sempowski, G.D.,Khurana, S.,Wiehe, K.,Saunders, K.O.,Acharya, P.,Haynes, B.F.,Baric, R.S.
A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.
Sci Transl Med, 14:eabj7125-eabj7125, 2022

PubMed Abstract: Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV; bat coronaviruses WIV-1 and RsSHC014; and SARS-CoV-2 variants D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, B.1.617.1, and B.1.617.2 by a receptor binding domain (RBD)–specific human antibody, DH1047. Prophylactic and therapeutic treatment with DH1047 was protective against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B.1.351 infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among sarbecoviruses. Thus, DH1047 is a broadly protective antibody that can prevent infection and mitigate outbreaks caused by SARS-related strains and SARS-CoV-2 variants. Our results also suggest that the conserved RBD epitope bound by DH1047 is a rational target for a universal sarbecovirus vaccine.

PubMed: 34726473
DOI: 10.1126/scitranslmed.abj7125

Experimental method

ELECTRON MICROSCOPY (3.43 Å)