{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:42:49Z","timestamp":1792032169454,"version":"4.4.0"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01AR074627-01A1"],"award-info":[{"award-number":["R01AR074627-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Serine protease inhibitors, SERPINS, are a highly conserved family of proteins that regulate serine proteases in the central coagulation and immune pathways, representing 2\u201310% of circulating proteins in the blood. Serine proteases form cascades of sequentially activated enzymes that direct thrombosis (clot formation) and thrombolysis (clot dissolution), complement activation in immune responses and also programmed cell death (apoptosis). Virus-derived serpins have co-evolved with mammalian proteases and serpins, developing into highly effective inhibitors of mammalian proteolytic pathways. Through interacting with extracellular and intracellular serine and cysteine proteases, viral serpins provide a new class of highly active virus-derived coagulation-, immune-, and apoptosis-modulating drug candidates. Viral serpins have unique characteristics: (1) function at micrograms per kilogram doses; (2) selectivity in targeting sites of protease activation; (3) minimal side effects at active concentrations; and (4) the demonstrated capacity to be modified, or fine-tuned, for altered protease targeting. To date, the virus-derived serpin class of biologics has proven effective in a wide range of animal models and in one clinical trial in patients with unstable coronary disease. Here, we outline the known viral serpins and review prior studies with viral serpins, considering their potential for application as new sources for immune-, coagulation-, and apoptosis-modulating therapeutics.<\/jats:p>","DOI":"10.3390\/biom13091393","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:12:21Z","timestamp":1694931141000},"page":"1393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Viral SERPINS\u2014A Family of Highly Potent Immune-Modulating Therapeutic Proteins"],"prefix":"10.3390","volume":"13","author":[{"given":"Kyle","family":"Varkoly","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, McLaren Macomb Hospital, Michigan State University College of Human Medicine, 1000 Harrington St., Mt Clemens, MI 48043, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Beladi","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Ascension Providence Hospital, Michigan State University College of Human Medicine, 16001 W Nine Mile Rd., Southfield, MI 48075, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Hamada","sequence":"additional","affiliation":[{"name":"College of Medicine, Kansas City University, 1750 Independence Ave, Kansas City, MO 64106, USA"},{"name":"Center for Immunotherapy Vaccines and Virotherapy, Biodesign Institute, Arizona State University, 727 E Tyler St., Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-3526","authenticated-orcid":false,"given":"Grant","family":"McFadden","sequence":"additional","affiliation":[{"name":"Center for Immunotherapy Vaccines and Virotherapy, Biodesign Institute, Arizona State University, 727 E Tyler St., Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-6356","authenticated-orcid":false,"given":"James","family":"Irving","sequence":"additional","affiliation":[{"name":"UCL Respiratory and the Institute of Structural and Molecular Biology, University College London, 5 University Street, London WC1E 6JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra R.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Center for Immunotherapy Vaccines and Virotherapy, Biodesign Institute, Arizona State University, 727 E Tyler St., Tempe, AZ 85287, USA"},{"name":"Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, 727 E Tyler St., Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"648349","DOI":"10.3389\/fcvm.2021.648349","article-title":"Therapeutic SERPINs: Improving on Nature","volume":"8","author":"Maas","year":"2021","journal-title":"Front. 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