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TitleStructural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies.
Journal, issue, pagesStructure, Vol. 29, Issue 7, Page 655-663.e4, Year 2021
Publish dateJul 1, 2021
AuthorsGabriele 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 AbstractEmerging 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 linksStructure / PubMed:34111408 / PubMed Central
MethodsEM (single particle)
Resolution3.42 - 3.72 Å
Structure data

23506

7ls9

EMDB-23506, PDB-7ls9:
Cryo-EM structure of neutralizing antibody 1-57 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 3.42 Å

23507

7lss

EMDB-23507, PDB-7lss:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-7
Method: EM (single particle) / Resolution: 3.72 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL 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

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