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From Proteopedia
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== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | 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 | + | 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. |
| - | Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.,Lee J, Zepeda SK, Park YJ, Taylor AL, Quispe J, Stewart C, Leaf EM, Treichel C, Corti D, King NP, Starr TN, Veesler D Cell Host Microbe. 2023 | + | Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.,Lee J, Zepeda SK, Park YJ, Taylor AL, Quispe J, Stewart C, Leaf EM, Treichel C, Corti D, King NP, Starr TN, Veesler D Cell Host Microbe. 2023 Dec 13;31(12):1961-1973.e11. doi: , 10.1016/j.chom.2023.10.018. Epub 2023 Nov 20. PMID:37989312<ref>PMID:37989312</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
PRD-0038 RBD bound to Rhinolophus alcyone ACE2 (local refinement)
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