{"doi":"10.1101/2023.09.26.559550","title":"Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo","abstract":"Abstract The rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His 10 epitope tag. In cultured cells, mutant ACE2 competitively inhibits lentiviral vectors pseudotyped with spike from multiple SARS-CoV-2 variants, and infectious SARS-CoV-2. Moreover, the protein can be nebulized and retains virus-binding properties. We developed a system for delivery of aerosolized ACE2 to K18-hACE2 mice and demonstrate protection by our modified ACE2 when delivered as a prophylactic agent. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents in vivo and suggest a new tool in the ongoing fight against SARS-CoV-2 and other ACE2-dependent viruses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400922,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":475598,"name":"Marley C. Caballero Van Dyke","orcid":"0000-0002-0332-9173","position":1,"is_corresponding":false},{"id":315752,"name":"Jennifer L. Eitson","orcid":null,"position":2,"is_corresponding":false},{"id":241071,"name":"Ian N. Boys","orcid":"0000-0002-0854-207X","position":3,"is_corresponding":false},{"id":241081,"name":"Matthew B. McDougal","orcid":"0000-0002-3957-8868","position":4,"is_corresponding":false},{"id":349032,"name":"Daniel M. Rosenbaum","orcid":"0000-0002-7174-4993","position":5,"is_corresponding":false},{"id":241087,"name":"John W. Schoggins","orcid":"0000-0002-7944-6800","position":6,"is_corresponding":false},{"id":484561,"name":"Daniel L. Kober","orcid":"0000-0001-8657-9348","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37808801","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":[]}