{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:05:35Z","timestamp":1785524735096,"version":"3.56.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004008","name":"Istituto Superiore di Sanit\u00e0","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004008","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    SARS\u2010CoV\u20102, like other positive\u2010sense RNA viruses, manipulates host lipid metabolism to facilitate its replication by enhancing lipogenesis and lipid droplet formation. This infection disrupts bioactive lipid levels associated with the inflammatory response by increasing nuclear factor\u2010\u03baB (NF\u2010\u03baB) transcription. Recent findings have shown that NF\u2010\u03baB activation is essential for sustaining SARS\u2010CoV\u20102 replication. Therefore, we proposed that counteracting NF\u2010\u03baB\u2013driven pro\u2010inflammatory lipid production could be accomplished by enhancing an anti\u2010inflammatory, lipolytic pathway. Our goal was to increase levels of Palmitoylethanolamide (PEA), the main activator of the Peroxisome Proliferator\u2010Activated Receptor\u2010\u03b1 (PPAR\u2010\u03b1), a transcription factor that suppresses lipogenesis and NF\u2010\u03baB transcription. PEA levels are mainly regulated by N\u2010acylethanolamine acid amidase (NAAA), a lysosomal enzyme that breaks down PEA. We hypothesized that inhibiting NAAA might interfere with SARS\u2010CoV\u20102 replication by allowing PEA to accumulate, thereby activating PPAR\u2010\u03b1 and suppressing NF\u2010\u03baB. Our results show that genetic or chemical ablation of NAAA significantly suppresses SARS\u2010CoV\u20102 replication\n                    <jats:italic>ex\u2010vivo<\/jats:italic>\n                    by 3 log\n                    <jats:sub>10<\/jats:sub>\n                    in human\u2010derived precision\u2010cut lung slices. We investigated whether inhibiting NAAA could block NF\u2010\u03baB activation by steering its opposite PPAR\u2010\u03b1 mediated pathway. We observed increased PPAR\u2010\u03b1 expression in NAAA KO cells, while PPAR\u2010\u03b1 expression remained low in infected untreated cells. Elevated PPAR\u2010\u03b1 expression correlated with reduced NF\u2010\u03baB activation when NAAA is ablated. These findings highlight NAAA as an essential host factor for SARS\u2010CoV\u20102 replication and propose a mechanism that reduces both replication and inflammation by targeting NF\u2010\u03baB during\n                    <jats:italic>Coronaviridae<\/jats:italic>\n                    replication.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70819","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T11:52:44Z","timestamp":1769255564000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N\u2010Acylethanolamine Acid Amidase Inhibition Reduces SARS\u2010CoV\u20102 Infection in Human Precision Cut\u2010Lung Slices and Downregulates NF\u2010KBB Signalling"],"prefix":"10.1002","volume":"98","author":[{"given":"Veronica","family":"La Rocca","sequence":"first","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"},{"name":"Human Technopole Viale Rita Levi\u2010Montalcini Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Filipponi","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"Diesendorf","sequence":"additional","affiliation":[{"name":"Institute of Virology University W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"De Carli","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Sciandrone","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Nottoli","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5488-605X","authenticated-orcid":false,"given":"Erika","family":"Plicanti","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Fonnesu","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Iacono","sequence":"additional","affiliation":[{"name":"Retrovirus Center, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Mengozzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Masi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Lenzi","sequence":"additional","affiliation":[{"name":"Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy"},{"name":"I.R.C.C.S. 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