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TitleRapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display.
Journal, issue, pagesCell Rep, Vol. 38, Issue 6, Page 110348, Year 2022
Publish dateFeb 8, 2022
AuthorsShiho Tanaka / C Anders Olson / Christopher O Barnes / Wendy Higashide / Marcos Gonzalez / Justin Taft / Ashley Richardson / Marta Martin-Fernandez / Dusan Bogunovic / Priyanthi N P Gnanapragasam / Pamela J Bjorkman / Patricia Spilman / Kayvan Niazi / Shahrooz Rabizadeh / Patrick Soon-Shiong /
PubMed AbstractThe increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or ...The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.
External linksCell Rep / PubMed:35114110 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.9 - 4.9 Å
Structure data

24786

7s0c

EMDB-24786, PDB-7s0c:
Structure of the SARS-CoV-2 S 6P trimer in complex with neutralizing antibody N-612-017
Method: EM (single particle) / Resolution: 3.25 Å

24787

7s0d

EMDB-24787, PDB-7s0d:
Structure of the SARS-CoV-2 S 6P trimer in complex with neutralizing antibody N-612-014
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-24788:
Structure of the SARS-CoV-2 S1 subunit in complex with antibody N-612-004
Method: EM (single particle) / Resolution: 4.9 Å

PDB-7s0b:
Structure of the SARS-CoV-2 RBD in complex with neutralizing antibody N-612-056
Method: X-RAY DIFFRACTION / Resolution: 2.9 Å

Chemicals

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

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Antibody / SARS-CoV-2 / COVID-19 / mRNA Display / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / Spike glycoprotein

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