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Article

Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications

1
Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500 Rio-Patras, Greece
2
Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece
3
Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 41500 Larissa, Greece
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(16), 5807; https://doi.org/10.3390/ijms21165807
Received: 17 June 2020 / Revised: 10 August 2020 / Accepted: 11 August 2020 / Published: 13 August 2020
While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors. Based on the clinical observation of low prevalence of smoking among hospitalized COVID-19 patients, we examined and identified a “toxin-like” amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375–390), which is homologous to a sequence of the Neurotoxin homolog NL1, one of the many snake venom toxins that are known to interact with nicotinic acetylcholine receptors (nAChRs). 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. We also performed computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 Spike Glycoprotein and the extracellular domain of the nAChR α9 subunit. We identified a main interaction between the aa 381–386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189–192 of the extracellular domain of the nAChR α9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the α9 nAChR and α-bungarotoxin. A similar interaction was observed between the pentameric α7 AChR chimera and SARS-CoV-2 Spike Glycoprotein. The findings raise the possibility that SARS-CoV-2 may interact with nAChRs, supporting the hypothesis of dysregulation of the nicotinic cholinergic system being implicated in the pathophysiology of COVID-19. Nicotine and other nicotinic cholinergic agonists may protect nAChRs and thus have therapeutic value in COVID-19 patients. View Full-Text
Keywords: COVID-19; SARS-CoV-2; smoking; nicotine; nicotinic cholinergic system; inflammation; acetylcholine receptors COVID-19; SARS-CoV-2; smoking; nicotine; nicotinic cholinergic system; inflammation; acetylcholine receptors
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MDPI and ACS Style

Farsalinos, K.; Eliopoulos, E.; Leonidas, D.D.; Papadopoulos, G.E.; Tzartos, S.; Poulas, K. Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications. Int. J. Mol. Sci. 2020, 21, 5807. https://doi.org/10.3390/ijms21165807

AMA Style

Farsalinos K, Eliopoulos E, Leonidas DD, Papadopoulos GE, Tzartos S, Poulas K. Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications. International Journal of Molecular Sciences. 2020; 21(16):5807. https://doi.org/10.3390/ijms21165807

Chicago/Turabian Style

Farsalinos, Konstantinos, Elias Eliopoulos, Demetres D. Leonidas, Georgios E. Papadopoulos, Socrates Tzartos, and Konstantinos Poulas. 2020. "Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications" International Journal of Molecular Sciences 21, no. 16: 5807. https://doi.org/10.3390/ijms21165807

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