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Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins

  • Lagoumintzis, George1
  • Chasapis, Christos T.1
  • Alexandris, Nikolaos1
  • Kouretas, Dimitrios2
  • Tzartos, Socrates1, 3
  • Eliopoulos, Elias4
  • Farsalinos, Konstantinos1
  • Poulas, Konstantinos1
  • 1 Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500, Rio-Patras, Greece
  • 2 Department of Biochemistry and Biotechnology, Faculty of Animal Physiology -Toxicology, University of Thessaly, Larissa, Greece
  • 3 Tzartos NeuroDiagnostics, 3, Eslin Street, Athens, 115 23, Greece
  • 4 Department of Biotechnology, Laboratory of Genetics, Agricultural University of Athens, Iera Odos 75, 11855, Athens, Greece
Published Article
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Publication Date
Jan 24, 2021
DOI: 10.1016/j.fct.2021.112009
PMID: 33503469
PMCID: PMC7830272
PubMed Central


SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. Studies have shown that smokers are less likely to be diagnosed with or be hospitalized for COVID-19 but, once hospitalized, have higher odds for an adverse outcome. 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. This epitope coincides with the well-described cryptic epitope for the human anti-SARS-CoV antibody CR3022. 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 model of the human α7 nAChR. We found that all studied protein complexes' interface 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. Our findings provide further support to the hypothesis about the protective role of nicotine and other cholinergic agonists. The potential therapeutic role of CR3022 and other similar monoclonal antibodies with increased affinity for SARS-CoV-2 Spike glycoprotein against the clinical effects originating from the dysregulated cholinergic pathway should be further explored.

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