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

• Published in: Obesity medicine Vol. 19; p. 100281
• Main Authors: AbdelMassih, Antoine Fakhry, Ye, Jianping, Kamel, Aya, Mishriky, Fady, Ismail, Habiba-Allah, Ragab, Heba Amin, El Qadi, Layla, Malak, Lauris, Abdu, Mariam, El-Husseiny, Miral, Ashraf, Mirette, Hafez, Nada, AlShehry, Nada, El-Husseiny, Nadine, AbdelRaouf, Nora, Shebl, Noura, Hafez, Nouran, Youssef, Nourhan, Afdal, Peter, Hozaien, Rafeef, Menshawey, Rahma, Saeed, Rana, Fouda, Raghda
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2020
• Subjects: Chinese herbals; COVID-19; Endothelial pathogenicity; Furin; Ion channel inhibitors; Polybasic cleavage site; Review; COVID-19; Furin; Endothelial pathogenicity; Chinese herbals; Ion channel inhibitors; Polybasic cleavage site
• ISSN: 2451-8476; 2451-8476
• DOI: 10.1016/j.obmed.2020.100281

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. •1-SARS-CoV-2 harbors a polybasic cleavage site.•2-This polybasic cleavage site leads to its canonical activation by a cellular enzyme termed Furin.•3-Furin is highly expressed in Endothelial, leading to endothelitis and vascular inflammation in COVID-19.•4-This also explains the augmented manifestations of COVID-19 in Obese and Diabetic patients.•5-The use of Chinese herbals and ion channel inhibitors can block the endothelial penetration of SARS-CoV-2.