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Title | Structural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies. |
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Journal, issue, pages | Structure, Vol. 29, Issue 7, Page 655-663.e4, Year 2021 |
Publish date | Jul 1, 2021 |
Authors | Gabriele Cerutti / Micah Rapp / Yicheng Guo / Fabiana Bahna / Jude Bimela / Eswar R Reddem / Jian Yu / Pengfei Wang / Lihong Liu / Yaoxing Huang / David D Ho / Peter D Kwong / Zizhang Sheng / Lawrence Shapiro / |
PubMed Abstract | Emerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively, show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against ...Emerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively, show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of the spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented an immune response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies, such as 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape. |
External links | Structure / PubMed:34111408 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.42 - 3.72 Å |
Structure data | EMDB-23506, PDB-7ls9: EMDB-23507, PDB-7lss: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Neutralizing antibody / Fusion protein / Spike glycoprotein / COVID-19 / RBD / RBD-directed antibody / 1-57 / Viral protein / IMMUNE SYSTEM / Viral Protein-IMMUNE SYSTEM complex / SARS-CoV-2 / spike / antibody |