COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprote
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DISCOVERY NOTES
Open Access
COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein Sepehr Ehsani1,2
Abstract The spike glycoprotein of the SARS-CoV-2 virus, which causes COVID-19, has attracted attention for its vaccine potential and binding capacity to host cell surface receptors. Much of this research focus has centered on the ectodomain of the spike protein. The ectodomain is anchored to a transmembrane region, followed by a cytoplasmic tail. Here we report a distant sequence similarity between the cysteine-rich cytoplasmic tail of the coronavirus spike protein and the hepcidin protein that is found in humans and other vertebrates. Hepcidin is thought to be the key regulator of iron metabolism in humans through its inhibition of the iron-exporting protein ferroportin. An implication of this preliminary observation is to suggest a potential route of investigation in the coronavirus research field making use of an already-established literature on the interplay of local and systemic iron regulation, cytokine-mediated inflammatory processes, respiratory infections and the hepcidin protein. The question of possible homology and an evolutionary connection between the viral spike protein and hepcidin is not assessed in this report, but some scenarios for its study are discussed. Keywords: Coronavirus, COVID-19, Cysteine, Ferroportin, Hepcidin, IL-6, Inflammation, Iron, Pufferfish, Sequence similarity, Spike protein
Findings Background
As of the beginning of October 2020, 189 countries and regions are tackling the challenge of the pandemic caused by the novel coronavirus, with more than 35 million confirmed cases of infection worldwide [23, 33]. Coronaviruses, first described in the 1960s [4, 82], are mostly present in birds and mammals, and there have thus far been seven known coronavirus infectious disease outbreaks in humans causing respiratory illness [62, 113]. The four strains causing mild or common-cold-like symptoms are called 229E, NL63, OC43 and HKU1. The first two strains are in the ‘alpha’ coronavirus subgroup, Correspondence: [email protected]; [email protected] 1 Theoretical and Philosophical Biology, Department of Philosophy, University College London, Bloomsbury, London WC1E 6BT, UK 2 Ronin Institute for Independent Scholarship, Montclair, NJ 07043, USA
whereas the latter two are ‘beta’ coronaviruses. The severe acute respiratory syndrome coronavirus (SARSCoV-1) of 2002, the Middle East respiratory syndrome coronavirus (MERS-CoV) of 2012, and now the SARSCoV-2 of 2019 (causing the ‘COVID-19’ disease that was declared a pandemic on 11 March 2020) are the remaining three known coronaviruses (all of the beta subgroup) causing severe human disease [6]. This positive-sense single-stranded RNA virus family possesses the structural proteins spike (S), membrane (M) and envelope (E) proteins, along with the nucleocapsid (N) protein. It also has the largest genome among RNA viruses [75]. Much research interest has been devoted to the sp
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