Version 1
: Received: 31 October 2023 / Approved: 31 October 2023 / Online: 31 October 2023 (14:53:01 CET)
Version 2
: Received: 12 February 2024 / Approved: 12 February 2024 / Online: 12 February 2024 (15:48:57 CET)
Ayyubova, G.; Gychka, S.G.; Nikolaienko, S.I.; Alghenaim, F.A.; Teramoto, T.; Shults, N.V.; Suzuki, Y.J. The Role of Furin in the Pathogenesis of COVID-19-Associated Neurological Disorders. Life 2024, 14, 279, doi:10.3390/life14020279.
Ayyubova, G.; Gychka, S.G.; Nikolaienko, S.I.; Alghenaim, F.A.; Teramoto, T.; Shults, N.V.; Suzuki, Y.J. The Role of Furin in the Pathogenesis of COVID-19-Associated Neurological Disorders. Life 2024, 14, 279, doi:10.3390/life14020279.
Ayyubova, G.; Gychka, S.G.; Nikolaienko, S.I.; Alghenaim, F.A.; Teramoto, T.; Shults, N.V.; Suzuki, Y.J. The Role of Furin in the Pathogenesis of COVID-19-Associated Neurological Disorders. Life 2024, 14, 279, doi:10.3390/life14020279.
Ayyubova, G.; Gychka, S.G.; Nikolaienko, S.I.; Alghenaim, F.A.; Teramoto, T.; Shults, N.V.; Suzuki, Y.J. The Role of Furin in the Pathogenesis of COVID-19-Associated Neurological Disorders. Life 2024, 14, 279, doi:10.3390/life14020279.
Abstract
Neurological disorders have been reported to occur in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may also exert long-term adverse neurological consequences. COVID-19 occurs due to the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between S1 subunit of the spike protein with the binding domain toward ACE2 and S2 subunit with transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein would also bind to and downregulate ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains a number of the spike protein molecules, furin-dependent cleavage would release a large number of free S1 proteins each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind the neurological disorders.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
