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However, the key factors influencing viral egress remain largely unclear. In this study, using transcription\u2010 and replication\u2010competent SARS\u2010CoV\u20102 virus\u2010like\u2010particle (SARS\u2010CoV\u20102 trVLP), electron microscopy, drug inhibition assays, and cellular pH\u2010sensitive fluorescent probes, we demonstrate that increased lysosomal exocytosis efficiency and lysosome deacidification play a pivotal role in facilitating SARS\u2010CoV\u20102 egress. Specifically, SARS\u2010CoV\u20102 may use multiple egress pathways, with lysosomal exocytosis as the primary mechanism and the biosynthetic secretory pathway as a less efficient route. Viral infection enhances lysosomal exocytosis via the ORF3a protein, thus facilitating viral release. SARS\u2010CoV\u20102 infection also induces lysosome deacidification; moreover, treatment with bafilomycin A1, which induces lysosome deacidification, further enhances viral egress. Furthermore, we systematically investigate how viral proteins affect lysosomal pH and enzymatic activities. Our findings reveal that ORF3a and E proteins induce lysosome deacidification and diminish lysosomal enzyme activities, probably protecting progeny viruses from premature cleavage and degradation. This study provides mechanistic insight into how SARS\u2010CoV\u20102 promotes lysosomal exocytosis and triggers lysosome deacidification for viral release.<\/jats:p>","DOI":"10.1002\/mlf2.70065","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T07:00:53Z","timestamp":1782457253000},"page":"339-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS\u2010CoV\u20102 enhances lysosomal exocytosis and deacidifies lysosomes to facilitate viral release"],"prefix":"10.1002","volume":"5","author":[{"given":"Fujun","family":"Qin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 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