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This review highlights the dual roles of exogenous serine proteases, emphasizing neutrophil serine proteases (NSPs) that facilitate viral entry and promote disease progression while also contributing to antiviral defense by degrading viral glycoproteins. Additionally, the potential to modulate serine protease activity to boost host defenses will be discussed, offering both significant challenges and new opportunities for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/molecules31040670","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:55:47Z","timestamp":1771253747000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Double-Edged Sword: Extracellular Serine Proteases as Facilitators of Infection and Mediators of Immunity"],"prefix":"10.3390","volume":"31","author":[{"given":"Alua","family":"Shagirova","sequence":"first","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave. 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiya","family":"Allayarova","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave. 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiya","family":"Makhanova","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave. 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanbek","family":"Bekturgan","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave. 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-6558","authenticated-orcid":false,"given":"Timo","family":"Burster","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr Ave. 53, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Seth, S., Batra, J., and Srinivasan, S. 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