+Search query
-Structure paper
Title | Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus. |
---|---|
Journal, issue, pages | Cell Host Microbe, Vol. 31, Issue 12, Page 1961-1973.e11, Year 2023 |
Publish date | Dec 13, 2023 |
Authors | Jimin Lee / Samantha K Zepeda / Young-Jun Park / Ashley L Taylor / Joel Quispe / Cameron Stewart / Elizabeth M Leaf / Catherine Treichel / Davide Corti / Neil P King / Tyler N Starr / David Veesler / |
PubMed Abstract | Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. ...Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution. |
External links | Cell Host Microbe / PubMed:37989312 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.8 - 3.5 Å |
Structure data | EMDB-41784, PDB-8u0t: EMDB-41786: PRD-0038 RBD bound to R. alcyone ACE2 EMDB-41842, PDB-8u29: EMDB-41843: PRD-0038 Spike glycoprotein NTD |
Chemicals | ChemComp-NAG: ChemComp-ZN: |
Source |
|
Keywords | VIRAL PROTEIN / Sarbecoviruses / Spike glycoprotein / fusion protein / neutralizing antibodies / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / inhibitor |