7KZB

Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1antibodies

Summary for 7KZB

• Entry DOI: 10.2210/pdb7kzb/pdb
• Descriptor: Fab heavy chain of CR3014-C8 antibody, Fab light chain of CR3014-C8 antibody, Spike glycoprotein, ... (8 entities in total)
• Functional Keywords: covid19, sars-cov2, antibody, antiviral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 119746.71

Authors

Langley, D.B.,Christ, D. (deposition date: 2020-12-10, release date: 2021-02-03, Last modification date: 2024-11-06)

Primary citation

Rouet, R.,Mazigi, O.,Walker, G.J.,Langley, D.B.,Sobti, M.,Schofield, P.,Lenthall, H.,Jackson, J.,Ubiparipovic, S.,Henry, J.Y.,Abayasingam, A.,Burnett, D.,Kelleher, A.,Brink, R.,Bull, R.A.,Turville, S.,Stewart, A.G.,Goodnow, C.C.,Rawlinson, W.D.,Christ, D.
Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies.
Mabs, 13:1922134-1922134,

PubMed Abstract: Antibodies against coronavirus spike protein potently protect against infection and disease, but whether such protection can be extended to variant coronaviruses is unclear. This is exemplified by a set of iconic and well-characterized monoclonal antibodies developed after the 2003 SARS outbreak, including mAbs m396, CR3022, CR3014 and 80R, which potently neutralize SARS-CoV-1, but not SARS-CoV-2. Here, we explore antibody engineering strategies to change and broaden their specificity, enabling nanomolar binding and potent neutralization of SARS-CoV-2. Intriguingly, while many of the matured clones maintained specificity of the parental antibody, new specificities were also observed, which was further confirmed by X-ray crystallography and cryo-electron microscopy, indicating that a limited set of VH antibody domains can give rise to variants targeting diverse epitopes, when paired with a diverse VL repertoire. Our findings open up over 15 years of antibody development efforts against SARS-CoV-1 to the SARS-CoV-2 field and outline general principles for the maturation of antibody specificity against emerging viruses.

PubMed: 34024246
DOI: 10.1080/19420862.2021.1922134

Experimental method

X-RAY DIFFRACTION (2.83 Å)