Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.
Cell Host Microbe
; 31(12): 1961-1973.e11, 2023 Dec 13.
Article
in En
| MEDLINE
| ID: mdl-37989312
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. 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Chiroptera
/
Severe acute respiratory syndrome-related coronavirus
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Host Microbe
Journal subject:
MICROBIOLOGIA
Year:
2023
Type:
Article
Affiliation country:
United States