tetano
Editor, Senior Moderator
Cell Host Microbe
. 2023 Nov 16:S1931-3128(23)00422-5.
doi: 10.1016/j.chom.2023.10.018. Online ahead of print. Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus
Jimin Lee[SUP] 1 [/SUP], Samantha K Zepeda[SUP] 1 [/SUP], Young-Jun Park[SUP] 2 [/SUP], Ashley L Taylor[SUP] 3 [/SUP], Joel Quispe[SUP] 1 [/SUP], Cameron Stewart[SUP] 1 [/SUP], Elizabeth M Leaf[SUP] 4 [/SUP], Catherine Treichel[SUP] 4 [/SUP], Davide Corti[SUP] 5 [/SUP], Neil P King[SUP] 4 [/SUP], Tyler N Starr[SUP] 3 [/SUP], David Veesler[SUP] 6 [/SUP]
Affiliations
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 Rhinolophusalcyone 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.
Keywords: ACE2; PRD-0038; SARS-CoV-2; bat coronaviruses; clade 3 sarbecovirus; cryo-EM; receptor tropism; spike glycoprotein; vaccine; zoonotic spillover.
. 2023 Nov 16:S1931-3128(23)00422-5.
doi: 10.1016/j.chom.2023.10.018. Online ahead of print. Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus
Jimin Lee[SUP] 1 [/SUP], Samantha K Zepeda[SUP] 1 [/SUP], Young-Jun Park[SUP] 2 [/SUP], Ashley L Taylor[SUP] 3 [/SUP], Joel Quispe[SUP] 1 [/SUP], Cameron Stewart[SUP] 1 [/SUP], Elizabeth M Leaf[SUP] 4 [/SUP], Catherine Treichel[SUP] 4 [/SUP], Davide Corti[SUP] 5 [/SUP], Neil P King[SUP] 4 [/SUP], Tyler N Starr[SUP] 3 [/SUP], David Veesler[SUP] 6 [/SUP]
Affiliations
- PMID: 37989312
- DOI: 10.1016/j.chom.2023.10.018
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 Rhinolophusalcyone 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.
Keywords: ACE2; PRD-0038; SARS-CoV-2; bat coronaviruses; clade 3 sarbecovirus; cryo-EM; receptor tropism; spike glycoprotein; vaccine; zoonotic spillover.