{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:15Z","timestamp":1787028435622,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u201ctoxin-like\u201d amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375\u2013390), 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 \u201ctoxin-like\u201d 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 \u03b19 subunit. We identified a main interaction between the aa 381\u2013386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189\u2013192 of the extracellular domain of the nAChR \u03b19 subunit, a region which forms the core of the \u201ctoxin-binding site\u201d of the nAChRs. The mode of interaction is very similar to the interaction between the \u03b19 nAChR and \u03b1-bungarotoxin. A similar interaction was observed between the pentameric \u03b17 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.<\/jats:p>","DOI":"10.3390\/ijms21165807","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T09:23:44Z","timestamp":1597310624000},"page":"5807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-4710","authenticated-orcid":false,"given":"Konstantinos","family":"Farsalinos","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500 Rio-Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0919-0571","authenticated-orcid":false,"given":"Elias","family":"Eliopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3874-2523","authenticated-orcid":false,"given":"Demetres D.","family":"Leonidas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios E.","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Socrates","family":"Tzartos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500 Rio-Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Poulas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500 Rio-Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","article-title":"Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1056\/NEJMsr2005760","article-title":"Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19","volume":"382","author":"Vaduganathan","year":"2020","journal-title":"N. 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