+Search query
-Structure paper
Title | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies. |
---|---|
Journal, issue, pages | MAbs, Vol. 13, Issue 1, Page 1922134, Year 2021 |
Publish date | May 28, 2021 |
![]() | Romain Rouet / Ohan Mazigi / Gregory J Walker / David B Langley / Meghna Sobti / Peter Schofield / Helen Lenthall / Jennifer Jackson / Stephanie Ubiparipovic / Jake Y Henry / Arunasingam Abayasingam / Deborah Burnett / Anthony Kelleher / Robert Brink / Rowena A Bull / Stuart Turville / Alastair G Stewart / Christopher C Goodnow / William D Rawlinson / Daniel Christ / ![]() |
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 ...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. |
![]() | ![]() ![]() ![]() |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.69 - 4.6 Å |
Structure data | ![]() EMDB-23111: ![]() EMDB-23112: ![]() EMDB-23113: ![]() PDB-7kza: ![]() PDB-7kzb: ![]() PDB-7kzc: |
Chemicals | ![]() ChemComp-CL: ![]() ChemComp-GOL: ![]() ChemComp-NA: ![]() ChemComp-PO4: ![]() ChemComp-HOH: |
Source |
|
![]() | IMMUNE SYSTEM / COVID19 / SARS-CoV2 / antibody / ANTIVIRAL PROTEIN / VIRAL PROTEIN/Immune System / VIRAL PROTEIN-Immune System complex |