{"doi":"10.1101/2020.05.18.102087","title":"Controlling the SARS-CoV-2 Spike Glycoprotein Conformation","abstract":"The coronavirus (CoV) viral host cell fusion spike (S) protein is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. We found that despite overall similarity in domain organization, different β-CoV strains display distinct S-protein configurations. Based on this analysis, we developed two soluble ectodomain constructs in which the highly immunogenic and mobile receptor binding domain (RBD) is locked in either the all-RBDs 'down' position or is induced to display a previously unobserved in SARS-CoV-2 2-RBDs 'up' configuration. These results demonstrate that the conformation of the S-protein can be controlled via rational design and provide a framework for the development of engineered coronavirus spike proteins for vaccine applications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118528,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":227358,"name":"Robert J. Edwards","orcid":"0000-0003-4446-1194","position":1,"is_corresponding":false},{"id":227359,"name":"Katayoun Mansouri","orcid":"0000-0001-6232-7330","position":2,"is_corresponding":false},{"id":227360,"name":"Katarzyna Janowska","orcid":"0000-0002-7936-2244","position":3,"is_corresponding":false},{"id":227361,"name":"Victoria Stalls","orcid":"0000-0002-1878-0581","position":4,"is_corresponding":false},{"id":231054,"name":"S. Gobeil","orcid":"0000-0002-0057-2477","position":5,"is_corresponding":false},{"id":227362,"name":"Megan Kopp","orcid":"0000-0002-6151-1571","position":6,"is_corresponding":false},{"id":227364,"name":"Allen L. Hsu","orcid":"0000-0003-2065-3802","position":7,"is_corresponding":false},{"id":227365,"name":"Mario J. Borgnia","orcid":"0000-0001-9159-1413","position":8,"is_corresponding":false},{"id":229643,"name":"Rob Parks","orcid":null,"position":9,"is_corresponding":false},{"id":96347,"name":"Barton F. Haynes","orcid":"0000-0002-7643-9023","position":10,"is_corresponding":false},{"id":227366,"name":"Priyamvada Acharya","orcid":"0000-0002-0089-277X","position":11,"is_corresponding":false},{"id":227357,"name":"Rory Henderson","orcid":"0000-0002-4301-6382","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:13:58.531532Z","pmid":"32511343","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}