Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Nicotinic Cholinergic System and COVID-19: Identification of a Potentially Crucial Snake Toxin-Like Sequence in the SARS-CoV-2 Spike Glycoprotein

Version 1 : Received: 17 May 2020 / Approved: 18 May 2020 / Online: 18 May 2020 (11:51:44 CEST)

How to cite: Farsalinos, K.; Eliopoulos, E.; Tzartos, S.; Poulas, K. Nicotinic Cholinergic System and COVID-19: Identification of a Potentially Crucial Snake Toxin-Like Sequence in the SARS-CoV-2 Spike Glycoprotein. Preprints 2020, 2020050301 (doi: 10.20944/preprints202005.0301.v1). Farsalinos, K.; Eliopoulos, E.; Tzartos, S.; Poulas, K. Nicotinic Cholinergic System and COVID-19: Identification of a Potentially Crucial Snake Toxin-Like Sequence in the SARS-CoV-2 Spike Glycoprotein. Preprints 2020, 2020050301 (doi: 10.20944/preprints202005.0301.v1).

Abstract

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

Subject Areas

COVID-19; SARS-CoV-2; smoking; nicotine; nicotinic cholinergic system; inflammation

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