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TitleAntibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking.
Journal, issue, pagesImmunity, Vol. 56, Issue 10, Page 2442-22455.e8, Year 2023
Publish dateOct 10, 2023
AuthorsLihong Liu / Ryan G Casner / Yicheng Guo / Qian Wang / Sho Iketani / Jasper Fuk-Woo Chan / Jian Yu / Bernadeta Dadonaite / Manoj S Nair / Hiroshi Mohri / Eswar R Reddem / Shuofeng Yuan / Vincent Kwok-Man Poon / Chris Chung-Sing Chan / Kwok-Yung Yuen / Zizhang Sheng / Yaoxing Huang / Jesse D Bloom / Lawrence Shapiro / David D Ho /
PubMed AbstractSARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we ...SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.1 intranasally. Structurally, both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, uncovering a site of vulnerability on SARS-CoV-2 spike. These antibodies prevented viral receptor engagement by locking the receptor-binding domain (RBD) of spike in the down conformation, revealing a mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but such mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.
External linksImmunity / PubMed:37776849 / PubMed Central
MethodsEM (single particle)
Resolution3.09 Å
Structure data

26583

7ukl

EMDB-26583, PDB-7ukl:
Cryo-EM structure of Antibody 12-16 in complex with prefusion SARS-CoV-2 Spike glycoprotein
Method: EM (single particle) / Resolution: 3.09 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Neutralizing Antibody / Viral Fusion Protein / SARS-CoV-2 / VIRAL PROTEIN-IMMUNE SYSTEM complex

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