A multicenter consensus: A role of furin in the endothelial tropism in obese patients with COVID-19 infection

Abstract

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.

The potential use of ABO blood group system for risk stratification of COVID-19

“…Specifically, some viruses harboring multi-basic cleavage sites in their protein sequence can be activated canonically with Furin. AbdelMassih and colleagues underlined the importance of Furin as a determinant of endothelial pathogenicity of SARS-CoV-2 [16] . Furin has gained interest in the past years as an important core player of metabolic syndrome, and little if no studies have explored its levels according to ABO blood groups.…”

Friend or foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment

“…The spike protein of SARS-CoV-2 contains a furin cleavage site, the unique RRAR motif; which was not found in any other subtype B betacoronavirus ( 30 ). Male and elder people, as well as obese and diabetic patients, have increased levels of furin in their blood ( 6 ), making this enzyme a potential therapeutic target of COVID-19 in those subjects ( 6 , 30 ). It is worth to test whether furin inhibitors, including the flavone Luteolin, isolated from Chinese herbal medicine ( 31 ), can prevent the COVID-19 infection and virus replication.…”

“…A recent study indicates that the diabetes drug metformin is able to reduce the mortality rate in the COVID-19 patients ( 3 ). Intensive investigations have been conducted in exploring the relationship between obesity and the severity of COVID-19 ( 4 , 5 , 6 ). Here we would like to present a commentary on the use of the two categories of therapeutic agents in COVID-19 patients with metabolic disorders including obesity, T2D and CVD.…”

COVID-19 during pregnancy should we really worry from vertical transmission or rather from fetal hypoxia and placental insufficiency? A systematic review and meta -analysis

“…The vascular tropism of COVID-19 has recently gained so much interest, and many of its multi-organ manifestations has been attributed to its endothelial tropism. Such endothelial tropism is accounted for by the high load of Angiotensin Converting Enzyme 2 (ACE2) and Furin, 11,12 which are important viral checkpoints, in the endothelium. Placenta is a vascular organ, whereby Furin play an important role in its differentiation, moreover, ACE2 and Angiotensin 1-7 are heavily expressed in the placenta, making the placenta an important target for the vascular tropic effect of COVID-19.…”