eprintid: 10178194 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/17/81/94 datestamp: 2023-10-05 10:57:25 lastmod: 2023-10-05 10:57:25 status_changed: 2023-10-05 10:57:25 type: article metadata_visibility: show sword_depositor: 699 creators_name: Varkoly, Kyle creators_name: Beladi, Roxana creators_name: Hamada, Mostafa creators_name: McFadden, Grant creators_name: Irving, James creators_name: Lucas, Alexandra R title: Viral SERPINS—A Family of Highly Potent Immune-Modulating Therapeutic Proteins ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: K71 keywords: Serpin; virus; immune-modulating; coagulation; apoptosis; poxvirus; plant virus; baculovirus; biologic note: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). abstract: Serine protease inhibitors, SERPINS, are a highly conserved family of proteins that regulate serine proteases in the central coagulation and immune pathways, representing 2–10% 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. date: 2023-09 date_type: published publisher: MDPI AG official_url: https://doi.org/10.3390/biom13091393 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2092247 doi: 10.3390/biom13091393 lyricists_name: Irving, James lyricists_id: JIRVI83 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner full_text_status: public publication: Biomolecules volume: 13 number: 9 article_number: 1393 issn: 2218-273X citation: Varkoly, Kyle; Beladi, Roxana; Hamada, Mostafa; McFadden, Grant; Irving, James; Lucas, Alexandra R; (2023) Viral SERPINS—A Family of Highly Potent Immune-Modulating Therapeutic Proteins. Biomolecules , 13 (9) , Article 1393. 10.3390/biom13091393 <https://doi.org/10.3390/biom13091393>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10178194/1/Irving_Viral%20SERPINS.%20A%20Family%20of%20Highly%20Potent%20Immune%20Modulating%20Therapeutic%20Proteins_VoR.pdf