RT Journal Article SR Electronic T1 COVID-19 and Cholinergic Anti-inflammatory Pathway: In silico Identification of an Interaction between α7 Nicotinic Acetylcholine Receptor and the Cryptic Epitopes of SARS-CoV and SARS-CoV-2 Spike Glycoproteins JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.20.259747 DO 10.1101/2020.08.20.259747 A1 George Lagoumintzis A1 Christos T. Chasapis A1 Nikolaos Alexandris A1 Socrates Tzartos A1 Elias Eliopoulos A1 Konstantinos Farsalinos A1 Konstantinos Poulas YR 2020 UL http://biorxiv.org/content/early/2020/08/21/2020.08.20.259747.abstract AB 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 α7 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 α7 nAChR.Competing Interest StatementThe authors have declared no competing interest.aaAmino AcidsARDSAcute Respiratory Distress SyndromeACE2Angiotensin Converting Enzyme 2COVID-19Corona Virus Disease 2019ECDExtracellular DomainLBDLigand-binding domainnAChRNicotinic Acetylcholine ReceptorNCSNicotinic Cholinergic SystemRBDReceptor Binding DomainSARS-CoVSevere Acute Respiratory Syndrome CoronavirusSARS-CoV-2Severe Acute Respiratory Syndrome Coronavirus 2.