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bioRxiv · 10.1101/2020.08.20.259747

COVID-19 and Cholinergic Anti-inflammatory Pathway: In silico Identification of an Interaction between alpha7 Nicotinic Acetylcholine Receptor and the Cryptic Epitopes of SARS-CoV and SARS-CoV-2 Spike Glycoproteins

Lagoumintzis, G.·Chasapis, C.·Alexandris, N.·Tzartos, S.·Eliopoulos, E.·Farsalinos, K.·Poulas, K.
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Abstract

SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. The observation of a low prevalence of smokers among hospitalized COVID-19 patients has led to the development of a hypothesis that nicotine could have protective effects by enhancing the cholinergic anti-inflammatory pathway. Based on clinical data and on modelling and docking experiments we have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a "toxin-like" epitope on the Spike Glycoprotein, with homology to a sequence of a snake venom toxin. We here present that this epitope coincides with the well-described cryptic epitope for the human antibody CR3022 and with the epitope for the recently described COVA1-16 antibody. Both antibodies are recognizing neighboring epitopes, are not interfering with the ACE2 protein and are not able to inhibit SARS-CoV and SARS-CoV-2 infections. In this study we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike Glycoproteins, at their open or closed conformations, with the molecular model of the human 7 nAChR. We found that the interface of all studied protein complexes involves a large part of the "toxin-like" sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human 7 nAChR.

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Lagoumintzis, G., Chasapis, C., Alexandris, N., Tzartos, S., Eliopoulos, E., Farsalinos, K., Poulas, K.. 2020-08-21. COVID-19 and Cholinergic Anti-inflammatory Pathway: In silico Identification of an Interaction between alpha7 Nicotinic Acetylcholine Receptor and the Cryptic Epitopes of SARS-CoV and SARS-CoV-2 Spike Glycoproteins. https://doi.org/10.1101/2020.08.20.259747

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