7RNJ

S2P6 Fab fragment bound to the SARS-CoV/SARS-CoV-2 spike stem helix peptide

Summary for 7RNJ

• Entry DOI: 10.2210/pdb7rnj/pdb
• Descriptor: Monoclonal antibody S2P6 Fab light chain, Monoclonal antibody S2P6 Fab heavy chain, Spike glycoprotein stem helix peptide, ... (5 entities in total)
• Functional Keywords: covid-19, sars-cov-2, neutralizing monoclonal antibody, viral protein-immune system complex, antiviral protein, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 49439.05

Authors

Snell, G.,Czudnochowski, N.,Croll, T.I.,Nix, J.C.,Corti, D.,Cameroni, E.,Pinto, D.,Beltramello, M.,Sauer, M.M.,Veesler, D. (deposition date: 2021-07-29, release date: 2021-08-11, Last modification date: 2024-11-06)

Primary citation

Pinto, D.,Sauer, M.M.,Czudnochowski, N.,Low, J.S.,Tortorici, M.A.,Housley, M.P.,Noack, J.,Walls, A.C.,Bowen, J.E.,Guarino, B.,Rosen, L.E.,di Iulio, J.,Jerak, J.,Kaiser, H.,Islam, S.,Jaconi, S.,Sprugasci, N.,Culap, K.,Abdelnabi, R.,Foo, C.,Coelmont, L.,Bartha, I.,Bianchi, S.,Silacci-Fregni, C.,Bassi, J.,Marzi, R.,Vetti, E.,Cassotta, A.,Ceschi, A.,Ferrari, P.,Cippa, P.E.,Giannini, O.,Ceruti, S.,Garzoni, C.,Riva, A.,Benigni, F.,Cameroni, E.,Piccoli, L.,Pizzuto, M.S.,Smithey, M.,Hong, D.,Telenti, A.,Lempp, F.A.,Neyts, J.,Havenar-Daughton, C.,Lanzavecchia, A.,Sallusto, F.,Snell, G.,Virgin, H.W.,Beltramello, M.,Corti, D.,Veesler, D.
Broad betacoronavirus neutralization by a stem helix-specific human antibody.
Science, 373:1109-1116, 2021

PubMed Abstract: The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.

PubMed: 34344823
DOI: 10.1126/science.abj3321

Experimental method

X-RAY DIFFRACTION (2.67 Å)