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Obes Med. 2020 Sep;19:100281. doi: 10.1016/j.obmed.2020.100281. Epub 2020 Jul 15.

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

Obesity medicine

Antoine Fakhry AbdelMassih, Jianping Ye, Aya Kamel, Fady Mishriky, Habiba-Allah Ismail, Heba Amin Ragab, Layla El Qadi, Lauris Malak, Mariam Abdu, Miral El-Husseiny, Mirette Ashraf, Nada Hafez, Nada AlShehry, Nadine El-Husseiny, Nora AbdelRaouf, Noura Shebl, Nouran Hafez, Nourhan Youssef, Peter Afdal, Rafeef Hozaien, Rahma Menshawey, Rana Saeed, Raghda Fouda

Affiliations

  1. Pediatric Cardiology Unit, Pediatrics' Department, Faculty of Medicine, Cairo University, Egypt.
  2. Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  3. Student and Internship Research Program (Research Accessibility Team), Faculty of Medicine, Cairo University, Egypt.
  4. Faculty of Dentistry, Cairo University, Egypt.
  5. Pixagon Graphic Design Agency, Cairo, Egypt.
  6. University of Irvine California, USA.
  7. Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Pediatrics' Department, Faculty of Medicine, Cairo University, Egypt.

PMID: 32835124 PMCID: PMC7362855 DOI: 10.1016/j.obmed.2020.100281

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.

© 2020 Elsevier Ltd. All rights reserved.

Keywords: COVID-19; Chinese herbals; Endothelial pathogenicity; Furin; Ion channel inhibitors; Polybasic cleavage site

Conflict of interest statement

The authors declare that there is no conflict of interest.

References

  1. Biotechnol Appl Biochem. 1996 Dec;24(3):257-67 - PubMed
  2. Reumatol Clin (Engl Ed). 2021 Aug-Sep;17(7):371-375 - PubMed
  3. Mol Cell. 2020 May 21;78(4):779-784.e5 - PubMed
  4. Drug Dev Res. 2020 Nov;81(7):771-776 - PubMed
  5. Obes Med. 2020 Sep;19:100259 - PubMed
  6. Front Immunol. 2020 Jun 11;11:1359 - PubMed
  7. Age Ageing. 2020 Jul 1;49(4):501-515 - PubMed
  8. Cardiovasc Endocrinol Metab. 2020 Apr 20;9(3):121-124 - PubMed
  9. Obes Med. 2020 Sep;19:100245 - PubMed
  10. Cell Res. 2019 Sep;29(9):739-753 - PubMed
  11. Clin Transl Immunology. 2019 Aug 05;8(8):e1073 - PubMed
  12. Science. 2020 Jun 5;368(6495):1038-1039 - PubMed
  13. Scand J Immunol. 2015 Dec;82(6):539-46 - PubMed
  14. J Intern Med. 2018 Oct;284(4):377-387 - PubMed
  15. Cardiovasc Endocrinol Metab. 2020 Jun 11;9(3):110-120 - PubMed
  16. Sci Rep. 2018 Mar 26;8(1):5212 - PubMed
  17. Neoplasia. 2012 Nov;14(11):1032-42 - PubMed
  18. J Histochem Cytochem. 2004 May;52(5):567-79 - PubMed
  19. Antiviral Res. 2017 Jul;143:176-185 - PubMed
  20. Obes Med. 2020 Sep;19:100255 - PubMed
  21. Biol Chem. 2010 Sep;391(9):1105-12 - PubMed
  22. Biochem Soc Trans. 2007 Aug;35(Pt 4):780-3 - PubMed
  23. J Biol Chem. 1992 Aug 15;267(23):16396-402 - PubMed
  24. Cardiovasc Endocrinol Metab. 2020 Jun 11;9(3):102-107 - PubMed
  25. Diabetes. 1997 Aug;46(8):1296-304 - PubMed
  26. Trop Med Int Health. 2020 Mar;25(3):278-280 - PubMed
  27. Obes Med. 2020 Sep;19:100254 - PubMed
  28. Postgrad Med J. 2021 Apr;97(1146):234-238 - PubMed
  29. J Med Chem. 2014 Jan 9;57(1):29-41 - PubMed
  30. PLoS One. 2013 Aug 06;8(8):e70542 - PubMed
  31. Nature. 1992 Nov 26;360(6402):358-61 - PubMed
  32. Virus Evol. 2018 Dec 15;4(2):vey035 - PubMed
  33. Biochem Soc Trans. 2004 Jun;32(Pt3):397-402 - PubMed
  34. J Antimicrob Chemother. 2014 Aug;69(8):2123-31 - PubMed
  35. Antiviral Res. 2018 Nov;159:35-44 - PubMed
  36. Clin Microbiol Infect. 2020 Jun;26(6):729-734 - PubMed
  37. Kardiochir Torakochirurgia Pol. 2019 Oct;16(3):128-132 - PubMed

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