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Cellular senescence has been implicated as a key pathogenic mechanism. This study investigated the therapeutic potential of regorafenib, a previously characterized senomorphic drug, for severe COVID\u201019. SARS\u2010CoV\u20102 virus\u2010infected K18\u2010hACE2 mice, overexpressing the human ACE2 receptor, exhibited 100% mortality by 10\u2009days post infection. Regorafenib treatment significantly improved survival rates, approximately 43% remaining alive. Mechanistically, regorafenib effectively suppressed type I and II interferon and cytokine signaling. Notably, regorafenib inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, a key driver of the cytokine storm associated with severe COVID\u201019. Our findings elucidate the molecular mechanisms underlying therapeutic effects of regorafenib and suggest its potential use as a promising treatment option for severe COVID\u201019.<\/jats:p>","DOI":"10.1002\/2211-5463.70002","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T09:40:12Z","timestamp":1738575612000},"page":"427-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regorafenib as a potential drug for severe <scp>COVID<\/scp>\u201019: inhibition of inflammasome activation in mice"],"prefix":"10.1002","volume":"15","author":[{"given":"Ju Hwan","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Center Chungbuk National University Hospital  Cheongju Republic of 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