Nicotinic cholinergic system and COVID-19 : identification of a potentially crucial snake toxin-like sequence in the SARS-CoV-2 spike glycoprotein.
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Poulas, Konstantinos
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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 and that nicotine intake could have beneficial effects. 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 the Neurotoxin homolog NL1, one of the snake venom toxins that are known to interact with acetylcholine receptors. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein and the superposition of the modelled structure of the Neurotoxin homolog NL1 and the SARS-CoV-2 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. Such interactions may lead to uncontrolled immune response and cytokine storm, which is implicated in the pathophysiology of severe COVID-19.
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SARS-CoV-2, COVID-19, Inflammation, Nicotine