A multicenter consensus: A role of furin in the endothelial tropism in obese patients with COVID-19 infection.
A multicenter consensus: A role of furin in the endothelial tropism in obese patients with COVID-19 infection.
复制标题
DOI：
10.1016/j.obmed.2020.100281
复制
发表时间：
2020-09-01
期刊：
影响因子：
--
通讯作者：
Fouda, Raghda
中科院分区：
文献类型：
--
作者：
AbdelMassih, Antoine Fakhry;Ye, Jianping;Fouda, Raghda
呋喃西林是一种裂解酶，在代谢综合征的发病机制中受到越来越多的重视。它的切割作用是包括SARS-CoV-2在内的几种病毒内皮细胞致病的重要激活步骤。这种呋喃西林介导的内皮趋向性似乎是新冠肺炎多器官系统参与的基础；这一特征在旧版本的冠状病毒科中没有被认识到。肥胖和糖尿病患者、男性和老年人的血清Furin水平随着其细胞活性的增加而增加；这可能解释了为什么这些亚组面临与新冠肺炎相关的并发症和死亡风险增加的原因。相反，吸烟会降低细胞内呋喃西林的水平，这一发现可能是吸烟者新冠肺炎严重程度降低的原因。中草药木犀草素被认为是一种可能的呋喃西林抑制剂，此前曾成功用于治疗登革热。此外，呋喃西林的细胞内水平在很大程度上取决于细胞内离子的浓度，特别是钠、钾和镁。因此，使用离子通道抑制剂，如钙通道阻滞剂或钾通道阻滞剂，可以防止疾病早期的细胞转化。尼古丁贴片和秋水仙碱也被认为是潜在的治疗方法，因为呋喃西林介导的新冠肺炎抑制。
Furin, a cleavage enzyme, is increasingly recognized in the pathogenesis of metabolic syndrome. Its cleavage action is an essential activation step for the endothelial pathogenicity of several viruses including SARS-CoV-2. This Furin-mediated endothelial tropism seems to underlie the multi-organ system involvement of COVID-19; which is a feature that was not recognized in the older versions of coronaviridae. Obese and diabetic patients, males, and the elderly, have increased serum levels of Furin, with its increased cellular activity; this might explain why these subgroups are at an increased risk of COVID-19 related complications and deaths. In contrast, smoking decreases cellular levels of Furin, this finding may be at the origin of the decreased severity of COVID-19 in smokers. Chinese herbal derived luteolin is suggested to be putative Furin inhibitor, with previous success against Dengue Fever. Additionally, Furin intracellular levels are largely dependent on concentration of intracellular ions, notably sodium, potassium, and magnesium. Consequently, the use of ion channel inhibitors, such as Calcium Channel blockers or Potassium Channel blockers, can prevent cellular transfection early in the course of the illness. Nicotine patches and Colchicine have also been suggested as potential therapies due to Furin mediated inhibition of COVID-19.