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MoringaA (MA) is an anti\u2010influenza virus active compound isolated from Moringa seeds, which can inhibit influenza virus by activating the TFEB\u2010autophagic lysosomal pathway in host cells. In this study, we obtained exosomes from M2\u2010type macrophages and encapsulated and delivered MA (MA\u2010Exos), and we investigated the efficacy of MA\u2010Exos in antiviral and viral pneumonia in vivo and in vitro, respectively. In addition, we provided insights into the mechanism by which MA\u2010Exos regulates TFEB\u2010lysosomal autophagy by RNA sequencing. The MA\u2010Exos showed broad\u2010spectrum inhibition of IAV, and significant promotion of the autophagic lysosomal pathway. Meanwhile, we found that GCN5 gene and protein were significantly down\u2010regulated in IAV\u2010infected cells after MA\u2010Exos intervention, indicating its blocking the acetylation of TFEB by GCN5. In addition, MA\u2010Exos also significantly promoted autophagy in lung tissue cells of mice with viral pneumonia. MA\u2010Exos can inhibit and clear influenza virus by mediating the TFEB\u2010autophagy lysosomal pathway by a mechanism related to the down\u2010regulation of histone acetyltransferase GCN5. Our study provides a strategy for targeting MA\u2010Exos for the treatment of viral pneumonia from both antiviral and virus\u2010induced inflammation inhibition pathways.<\/jats:p>","DOI":"10.1002\/jmv.29906","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T01:12:59Z","timestamp":1726103579000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Broad\u2010spectrum antiviral effect of MoringaA\u2010loaded exosomes against IAV by mediating the GCN5\u2010TFEB\u2010autolysosome pathway"],"prefix":"10.1002","volume":"96","author":[{"given":"Chunmei","family":"Lv","sequence":"first","affiliation":[{"name":"Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy Zunyi Medical University Zunyi Guizhou China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education 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