Frank H. Netter M.D. School of Medicine at Quinnipiac University, North Haven, Connecticut, USA.
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Expert Opin Ther Targets. 2021 Jun;25(6):423-433. doi: 10.1080/14728222.2021.1944101. Epub 2021 Jun 25.
Defibrotide (DF) is a polyribonucleotide with antithrombotic, pro-fibrinolytic, and anti-inflammatory effects on endothelium. These effects and the established safety of DF present DF as a strong candidate to treat viral and post-infectious syndromes involving endothelial dysfunction.
We discuss DF and other therapeutic agents that have the potential to target endothelial components of pathogenesis in viral and post-infectious syndromes. We introduce defibrotide (DF), describe its mechanisms of action, and explore its established pleiotropic effects on the endothelium. We describe the established pathophysiology of Coronavirus Disease 2019 (COVID-19) and highlight the processes specific to COVID-19 potentially modulated by DF. We also present influenza A and viral hemorrhagic fevers, especially those caused by hantavirus, Ebola virus, and dengue virus, as viral syndromes in which DF might serve therapeutic benefit. Finally, we offer our opinion on novel treatment strategies targeting endothelial dysfunction in viral infections and their severe manifestations.
Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.
地夫可特(DF)是一种具有抗血栓、促纤维蛋白溶解和抗炎作用的多核苷酸,对内皮细胞有影响。这些作用以及 DF 的既定安全性使 DF 成为治疗涉及内皮功能障碍的病毒和感染后综合征的强有力候选药物。
我们讨论了 DF 和其他具有靶向病毒和感染后综合征发病机制内皮成分潜力的治疗剂。我们介绍了地夫可特(DF),描述了它的作用机制,并探讨了它对内皮的既定多效性作用。我们描述了 2019 年冠状病毒病(COVID-19)的既定病理生理学,并强调了 COVID-19 中可能由 DF 调节的特定过程。我们还介绍了甲型流感和病毒性出血热,特别是汉坦病毒、埃博拉病毒和登革热病毒引起的病毒性综合征,DF 可能对此类疾病有治疗作用。最后,我们对针对病毒感染及其严重表现的内皮功能障碍的新型治疗策略提出了我们的看法。
鉴于内皮功能障碍在许多感染性综合征中,特别是在 COVID-19 中的关键作用,这些疾病的治疗药理学应越来越重视内皮稳定。应进一步研究具有内皮保护特性的几种药物,将其作为严重病毒感染和血管炎的治疗方法,尤其是在其他治疗方法失败的情况下。