{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:56:46Z","timestamp":1790791006476,"version":"4.1.0"},"reference-count":68,"publisher":"Portland Press Ltd.","issue":"22","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,27]]},"abstract":"<jats:p>Exacerbated inflammation is a major contributor to tissue damage and mortality in infectious diseases, including SARS-CoV-2. The resolution phase of inflammation is critical for restoring tissue homeostasis following an injury. Annexin A1 (AnxA1) is a ubiquitous protein that plays a fundamental role in the resolution of inflammation, including in preclinical models of infectious disease. Here, we investigated the role of AnxA1 in coronavirus infection and its potential as a host-targeted therapeutic strategy against SARS-CoV-2. Wildtype (WT) and AnxA1 knockout (AnxA1KO) mice were intranasally infected with the murine betacoronavirus MHV-3 to study the endogenous role of AnxA1. Immunohistochemistry and Western blot analyses in the lungs of MHV-3-infected mice revealed increased AnxA1 expression and its cleavage, which was associated with neutrophilic infiltration (Ly6G+ cells) mainly in peribronchiolar and perivascular regions. AnxA1-deficient mice exhibited higher neutrophilic infiltration and lung damage, alongside increased CXCL1 production in the lungs, when compared with WT-infected mice. In a murine model of SARS-CoV-2 infection in K18-hACE2 mice, we found increased AnxA1 cleavage associated with lung inflammation. Treatment of SARS-CoV-2-infected K18-hACE2 mice with the AnxA1-mimetic peptide, Ac2-26, reduced lung damage and lethality, without altering the host ability to deal with viral replication. Notably, Ac2-26-treated mice exhibited similar levels of protection to that afforded by the nucleotide analog Remdesivir, following SARS-CoV-2 infection. Our findings highlight the protective role of the endogenous AnxA1 in mitigating coronavirus-induced lung inflammation and underscore the therapeutic potential of AnxA1 mimetic Ac2-26 as a host-targeted therapy against SARS-CoV-2.<\/jats:p>","DOI":"10.1042\/cs20255801","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T17:36:55Z","timestamp":1763401015000},"page":"1489-1505","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Annexin A1 as a key modulator of lung inflammation during coronavirus infections"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-6169","authenticated-orcid":false,"given":"Filipe","family":"Resende","sequence":"first","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"Martins Queiroz-Junior","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Roque","family":"Ascen\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian de Meira","family":"Chaves","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisse","family":"de Souza Barbosa Lacerda","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Rocha","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Teixeira","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Costa","sequence":"additional","affiliation":[{"name":"3Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talita","family":"Fonseca","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Gualberto","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Luiza","family":"de Castro Santos","sequence":"additional","affiliation":[{"name":"4Department of Phisiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenniffer","family":"Martins","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick Bryan","family":"de Sousa Lima","sequence":"additional","affiliation":[{"name":"5Signaling in Inflammation Laboratory, Departament of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelson H\u00e9ric","family":"Alves Monteiro","sequence":"additional","affiliation":[{"name":"5Signaling in Inflammation Laboratory, Departament of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Zaidan","sequence":"additional","affiliation":[{"name":"5Signaling in Inflammation Laboratory, Departament of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00eds C.","family":"Grossi","sequence":"additional","affiliation":[{"name":"5Signaling in Inflammation Laboratory, Departament of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Augusto","family":"Carvalho Costa","sequence":"additional","affiliation":[{"name":"4Department of Phisiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Amorim Beltrami","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirl\u00e2ndia P.","family":"Sousa","sequence":"additional","affiliation":[{"name":"5Signaling in Inflammation Laboratory, Departament of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Pires Goulart Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"4Department of Phisiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Campolina-Silva","sequence":"additional","affiliation":[{"name":"6Department of Obstetrics, Gynecology and Reproduction, Universit\u00e9 Laval, Quebec City, Qu\u00e9bec, Canada"},{"name":"7Reproduction, Mother and Youth Health Care Division, CRCHUQ-UL, Quebec City, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Pinho","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0175-642X","authenticated-orcid":false,"given":"Vivian V.","family":"Costa","sequence":"additional","affiliation":[{"name":"1Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"},{"name":"2Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"2025112715013183300_CS-2025-5801C1","doi-asserted-by":"crossref","DOI":"10.1186\/s12985-015-0439-5","article-title":"MERS coronavirus: diagnostics, epidemiology and transmission","volume":"12","author":"Mackay","year":"2015","journal-title":"Virol. 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