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Recent studies indicate that both blocking and promoting cell death negatively affect coronavirus replication, implying that coronaviruses may fine\u2010tune cell death pathways to optimize their propagation. However, the mechanisms underlying this remain poorly understood. Here, it is verified that coronaviruses induce the formation of a Z\u2010DNA\u2010binding protein 1 (ZBP1)\u2010initiated cell death complex involving ZBP1, Z\u2010RNA, receptor\u2010interacting serine\/threonine\u2010protein kinase 3 (RIPK3), and caspase\u20108, thereby triggering apoptosis, pyroptosis, and necroptosis in human bronchial epithelial cells. To impede the activation of apoptosis and pyroptosis, NSP5 and ORF6 of SARS\u2010CoV\u20102 concurrently inhibit caspase\u20108 activity by targeting its large and small subunits, respectively. Additionally, NSP13, the viral helicase, interacts with RIPK3 to impair its binding to ZBP1, thus suppressing ZBP1\u2010initiated necroptosis. This inhibitory effect on cell death is likely conserved across \u03b2\u2010coronaviruses. Furthermore, co\u2010infection of influenza A virus and SARS\u2010CoV\u20102 is demonstrated to exacerbate disease severity, although the mechanisms remain unclear. These findings suggest that \u03b2\u2010coronavirus\u2010induced inhibition of cell death enhances influenza A virus replication and worsens inflammation during their co\u2010infection, ultimately increasing mortality in mice. This research provides valuable insights into the regulation of coronavirus\u2010induced cell death, offering potential therapeutic strategies for combating highly pathogenic coronavirus infections.<\/jats:p>","DOI":"10.1002\/advs.202503977","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T13:45:32Z","timestamp":1755179132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The NSP5, ORF6 and NSP13 of SARS\u2010CoV\u20102 Cooperate to Modulate Inflammatory Cell Death Activation"],"prefix":"10.1002","volume":"12","author":[{"given":"Huan","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of infectious diseases Shenzhen Bay Laboratory  Shenzhen Guangdong 518132 China"},{"name":"Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation  Shenzhen Guangdong 518060 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