Viral SERPINS-A Family of Highly Potent Immune-Modulating Therapeutic Proteins.
Viral SERPINS-A Family of Highly Potent Immune-Modulating Therapeutic Proteins.
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DOI：
10.3390/biom13091393
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发表时间：
2023-09-15
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
丝氨酸蛋白酶抑制剂（SERPINS）是一种高度保守的蛋白质家族，在中枢凝血和免疫途径中调节丝氨酸蛋白酶，占血液中循环蛋白质的2-10%。丝氨酸蛋白酶形成连续激活的酶的级联，其指导血栓形成（凝块形成）和血栓溶解（凝块溶解）、免疫应答中的补体激活以及程序性细胞死亡（凋亡）。病毒来源的丝氨酸蛋白酶抑制剂与哺乳动物蛋白酶和丝氨酸蛋白酶抑制剂共同进化，发展成为哺乳动物蛋白水解途径的高效抑制剂。通过与细胞外和细胞内丝氨酸和半胱氨酸蛋白酶的相互作用，病毒丝氨酸蛋白酶抑制剂提供了一类新的高活性病毒衍生的凝血、免疫和凝血调节药物候选物。病毒丝氨酸蛋白酶抑制剂具有独特的特征：（1）以微克/千克剂量起作用;（2）在蛋白酶活化的靶向位点中的选择性;（3）在活性浓度下的最小副作用;以及（4）经证实的被修饰或微调以改变蛋白酶靶向的能力。迄今为止，病毒衍生的丝氨酸蛋白酶抑制剂类生物制剂已在广泛的动物模型和一项不稳定型冠状动脉疾病患者的临床试验中证明有效。在这里，我们概述了已知的病毒丝氨酸蛋白酶抑制剂和审查以前的研究与病毒丝氨酸蛋白酶抑制剂，考虑其潜在的应用作为新的来源免疫，凝血，和免疫调节疗法。
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.
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影响因子：
4.6
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