{"doi":"10.1016/j.celrep.2025.115760","title":"Designed miniproteins potently inhibit and protect against MERS-CoV","abstract":"Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins that bind with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the dipeptidylpeptidase 4 (DPP4) receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice, motivating its future clinical development as a next-generation countermeasure against this virus with pandemic potential.","journal":"Cell Reports","year":2025,"id":512548,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":97048,"name":"M. Alejandra Tortorici","orcid":"0000-0002-2260-2577","position":1,"is_corresponding":false},{"id":1038511,"name":"Nicholas J. Catanzaro","orcid":null,"position":2,"is_corresponding":false},{"id":294604,"name":"Amin Addetia","orcid":"0000-0001-6703-3841","position":3,"is_corresponding":false},{"id":218559,"name":"Brian Coventry","orcid":"0000-0002-6910-6255","position":4,"is_corresponding":false},{"id":620800,"name":"Heather M. Froggatt","orcid":"0000-0001-7785-0976","position":5,"is_corresponding":false},{"id":1034562,"name":"Jimin Lee","orcid":"0000-0001-5849-7732","position":6,"is_corresponding":false},{"id":828534,"name":"Cameron Stewart","orcid":"0000-0002-2786-6256","position":7,"is_corresponding":false},{"id":842554,"name":"Jack T Brown","orcid":"0000-0002-6159-2148","position":8,"is_corresponding":false},{"id":218558,"name":"Inna Goreshnik","orcid":"0000-0002-9254-9249","position":9,"is_corresponding":false},{"id":1334597,"name":"Jeremiah N Sims","orcid":null,"position":10,"is_corresponding":false},{"id":552252,"name":"Lukas F. Milles","orcid":"0000-0001-8417-3205","position":11,"is_corresponding":false},{"id":242363,"name":"Basile I. M. Wicky","orcid":"0000-0002-2501-7875","position":12,"is_corresponding":false},{"id":1113282,"name":"Matthias Glögl","orcid":"0000-0001-7011-8184","position":13,"is_corresponding":false},{"id":585355,"name":"Stacey Gerben","orcid":"0000-0003-0313-6248","position":14,"is_corresponding":false},{"id":268184,"name":"Alex Kang","orcid":"0000-0001-5487-0499","position":15,"is_corresponding":false},{"id":453451,"name":"Asim K. Bera","orcid":"0000-0001-9473-2912","position":16,"is_corresponding":false},{"id":1217522,"name":"William W. Sharkey","orcid":null,"position":17,"is_corresponding":false},{"id":105112,"name":"Alexandra Schäfer","orcid":null,"position":18,"is_corresponding":false},{"id":313892,"name":"Jack R. Harkema","orcid":"0000-0003-4682-0824","position":19,"is_corresponding":false},{"id":5952,"name":"Ralph S. Baric","orcid":"0000-0001-6827-8701","position":20,"is_corresponding":false},{"id":333886,"name":"David Baker","orcid":"0000-0002-6811-8238","position":21,"is_corresponding":false},{"id":97051,"name":"David Veesler","orcid":"0000-0002-6019-8675","position":22,"is_corresponding":false},{"id":838651,"name":"Robert J. Ragotte","orcid":"0000-0002-6463-1595","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:48:06.263458Z","pmid":"40450691","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":[]}