{"doi":"10.15252/emmm.202317376","title":"Viral anti‐inflammatory serpin reduces immuno‐coagulopathic pathology in SARS‐CoV‐2 mouse models of infection","abstract":"SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immuno-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immuno-coagulopathic responses, and Long COVID.","journal":"EMBO Molecular Medicine","year":2023,"id":357932,"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":0.9528,"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":456972,"name":"Yize Li","orcid":"0000-0003-1721-741X","position":1,"is_corresponding":false},{"id":883102,"name":"Karen V. Kibler","orcid":"0000-0002-2914-7319","position":2,"is_corresponding":false},{"id":456855,"name":"Simona Kraberger","orcid":"0000-0002-7037-9242","position":3,"is_corresponding":false},{"id":109879,"name":"Arvind Varsani","orcid":"0000-0003-4111-2415","position":4,"is_corresponding":false},{"id":1108050,"name":"Julie Turk","orcid":null,"position":5,"is_corresponding":false},{"id":1108051,"name":"Nora Elmadbouly","orcid":null,"position":6,"is_corresponding":false},{"id":747797,"name":"Emily Aliskevich","orcid":null,"position":7,"is_corresponding":false},{"id":1108052,"name":"Laurel Spaccarelli","orcid":null,"position":8,"is_corresponding":false},{"id":261562,"name":"Bereket Estifanos","orcid":null,"position":9,"is_corresponding":false},{"id":998113,"name":"Junior A. Enow","orcid":"0000-0002-4631-6989","position":10,"is_corresponding":false},{"id":979204,"name":"Isabela R. Zanetti","orcid":"0000-0002-3441-5955","position":11,"is_corresponding":false},{"id":1108053,"name":"Nicholas Saldevar","orcid":null,"position":12,"is_corresponding":false},{"id":260548,"name":"Efrem S. Lim","orcid":"0000-0002-3397-9310","position":13,"is_corresponding":false},{"id":1107735,"name":"Jessika Schlievert","orcid":"0009-0006-8886-2183","position":14,"is_corresponding":false},{"id":747795,"name":"Kyle Browder","orcid":null,"position":15,"is_corresponding":false},{"id":1108054,"name":"Anjali Wilson","orcid":null,"position":16,"is_corresponding":false},{"id":1108055,"name":"Fernando Arcos Juan","orcid":null,"position":17,"is_corresponding":false},{"id":1108056,"name":"Aubrey Pinteric","orcid":null,"position":18,"is_corresponding":false},{"id":1108057,"name":"Aman Garg","orcid":null,"position":19,"is_corresponding":false},{"id":1107736,"name":"Henna Monder","orcid":"0009-0001-5721-112X","position":20,"is_corresponding":false},{"id":1107737,"name":"Rohan Saju","orcid":"0009-0005-4590-6572","position":21,"is_corresponding":false},{"id":1107738,"name":"Savanah D. Gisriel","orcid":"0000-0002-3728-5826","position":22,"is_corresponding":false},{"id":630587,"name":"Bertram L. Jacobs","orcid":"0000-0002-9529-8107","position":23,"is_corresponding":false},{"id":838964,"name":"Timothy L. Karr","orcid":"0000-0002-4180-6583","position":24,"is_corresponding":false},{"id":634141,"name":"Esther Borges Florsheim","orcid":"0000-0002-5889-7442","position":25,"is_corresponding":false},{"id":315580,"name":"Vivek Kumar","orcid":"0000-0001-7536-9281","position":26,"is_corresponding":false},{"id":747794,"name":"J W Wallen","orcid":null,"position":27,"is_corresponding":false},{"id":388302,"name":"Masmudur M. Rahman","orcid":"0000-0002-7177-819X","position":28,"is_corresponding":false},{"id":388303,"name":"Grant McFadden","orcid":"0000-0002-2556-3526","position":29,"is_corresponding":false},{"id":260546,"name":"Brenda G. Hogue","orcid":"0000-0002-4545-9208","position":30,"is_corresponding":false},{"id":747291,"name":"Alexandra Lucas","orcid":"0000-0002-5195-1442","position":31,"is_corresponding":false},{"id":485394,"name":"Liqiang Zhang","orcid":"0000-0002-4175-7590","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"37534622","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":[]}