+Search query
-Structure paper
Title | Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking. |
---|---|
Journal, issue, pages | Immunity, Vol. 56, Issue 10, Page 2442-22455.e8, Year 2023 |
Publish date | Oct 10, 2023 |
Authors | Lihong 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 Abstract | 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 ...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 links | Immunity / PubMed:37776849 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.09 Å |
Structure data | EMDB-26583, PDB-7ukl: |
Chemicals | ChemComp-NAG: |
Source |
|
Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Neutralizing Antibody / Viral Fusion Protein / SARS-CoV-2 / VIRAL PROTEIN-IMMUNE SYSTEM complex |