{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:29:08Z","timestamp":1783978148849,"version":"3.55.0"},"reference-count":79,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M712244"],"award-info":[{"award-number":["2022M712244"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Continual evolution of SARS\u2010CoV\u20102 spike drives the emergence of Omicron variants that show increased spreading and immune evasion. Understanding how the variants orientate themselves towards host immune defence is crucial for controlling future pandemics. Herein, we demonstrate that human cathelicidin LL\u201037, a crucial component of innate immunity, predominantly binds to the S2 subunit of SARS\u2010CoV\u20102 spike protein, occupying sites where TMPRSS2 typically binds. This binding impedes TMPRSS2\u2010mediated priming at site S2' and subsequent membrane fusion processes. The mutation N764K within S2 subunit of Omicron variants reduces affinity for LL\u201037 significantly, thereby diminishing binding capacity and inhibitory effects on membrane fusion. Moreover, the early humoral immune response enhanced by LL\u201037 is observed in mice against SARS\u2010CoV\u20102 spike but not Omicron BA.4\/5 spike. These findings reveal the mechanism underlying interactions amongst LL\u201037, TMPRSS2 and SARS\u2010CoV\u20102 and VOCs, and highlight the distinct mutation for Omicron variants to evade the fusion activity inhibition by host innate immunity.<\/jats:p>","DOI":"10.1111\/cpr.70060","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T01:40:33Z","timestamp":1747359633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>LL\u201037<\/scp>\n                    Inhibits\n                    <scp>TMPRSS2<\/scp>\n                    \u2010Mediated\n                    <scp>S2<\/scp>\n                    ' Site Cleavage and\n                    <scp>SARS\u2010CoV\u20102<\/scp>\n                    Infection but Not Omicron Variants"],"prefix":"10.1111","volume":"58","author":[{"given":"Zhenfei","family":"Bi","sequence":"first","affiliation":[{"name":"Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"},{"name":"Department of Hepatobiliary Surgery, Xinqiao Hospital Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6333-8496","authenticated-orcid":false,"given":"Wenyan","family":"Ren","sequence":"additional","affiliation":[{"name":"Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu 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