{"doi":"10.1101/2020.03.26.010165","title":"Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies","abstract":"ABSTRACT The pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV-1) and COVID-19 coronavirus (SARS-CoV-2) have all emerged into the human population with devastating consequences. These viruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics to combat these highly pathogenic coronaviruses. Here, we describe the isolation and characterization of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs are capable of potently neutralizing MERS-CoV or SARS-CoV-1 S pseudotyped viruses. The crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs block receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S, and demonstrate that this cross-reactive VHH is capable of neutralizing SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118450,"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":77,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9642,"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":551424,"name":"Dorien De Vlieger","orcid":null,"position":1,"is_corresponding":false},{"id":87307,"name":"Kizzmekia S. Corbett","orcid":"0000-0002-2641-4688","position":2,"is_corresponding":false},{"id":488264,"name":"Gretel M. Torres","orcid":"0000-0002-1932-7383","position":3,"is_corresponding":false},{"id":550676,"name":"Wander Van Breedam","orcid":"0000-0001-7755-988X","position":4,"is_corresponding":false},{"id":550677,"name":"Kenny Roose","orcid":"0000-0002-5270-4603","position":5,"is_corresponding":false},{"id":550678,"name":"Loes van Schie","orcid":"0000-0003-2588-9750","position":6,"is_corresponding":false},{"id":551425,"name":"VIB-CMB COVID-19 Response Team","orcid":null,"position":7,"is_corresponding":false},{"id":241077,"name":"Markus Hoffmann","orcid":"0000-0003-4603-7696","position":8,"is_corresponding":false},{"id":241083,"name":"Stefan Pöhlmann","orcid":"0000-0001-6086-9136","position":9,"is_corresponding":false},{"id":87311,"name":"Barney S. Graham","orcid":"0000-0001-8112-0853","position":10,"is_corresponding":false},{"id":550679,"name":"Nico Callewaert","orcid":"0000-0003-2069-6917","position":11,"is_corresponding":false},{"id":550680,"name":"Bert Schepens","orcid":"0000-0002-2028-1984","position":12,"is_corresponding":false},{"id":550681,"name":"Xavier Saelens","orcid":"0000-0003-0686-0311","position":13,"is_corresponding":false},{"id":87312,"name":"Jason S. McLellan","orcid":"0000-0003-3991-542X","position":14,"is_corresponding":false},{"id":87305,"name":"Daniel Wrapp","orcid":"0000-0002-0538-9647","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:13:58.531532Z","pmid":null,"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":[]}