PDF(Pubmed)
Abstract：
Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.
摘要：
抑肽酶是人类蛋白酶的广谱抑制剂，由于其有效的抗纤维蛋白溶解作用，已被批准用于治疗单冠状动脉搭桥手术中的出血。在COVID-19大流行爆发后，迫切需要寻找新的抗病毒药物。抑肽酶是治疗性重新定位作为广谱抗病毒药物和治疗特征病毒性呼吸道疾病的症状过程的良好候选者。包括COVID-19。这是由于其强大的药理学能力，可以抑制呼吸道病毒在其感染机制中使用的过多宿主蛋白酶。蛋白酶允许组成其病毒衣壳的蛋白质的切割和构象变化，从而使它们能够通过识别上皮细胞中的靶标来锚定自己。此外,这些蛋白酶的激活会引发引发感染的炎症过程。药物的吸引力不仅在于其药效学特征，还在于通过吸入途径给药的可能性，避免不必要的系统性影响。这个,加上治疗费用低（约2欧元/剂），使其成为到达经济能力较低的国家的一个很好的候选人。在这篇文章中,我们将讨论药效学，药代动力学，和通过吸入途径给药的抑肽酶的毒理学特征；分析我们对这种药物的认识的主要进展；以及为了在治疗中重新定位这种药物在研究中应该采取的未来方向。
