{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:07:38Z","timestamp":1771657658372,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oyster Point Pharma, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the worldwide coronavirus disease 2019 (COVID-19) pandemic. Although the pathophysiology of SARS-CoV-2 infection is still being elucidated, the nicotinic cholinergic system may play a role. To evaluate the interaction of the SARS-CoV-2 virus with human nicotinic acetylcholine receptors (nAChRs), we assessed the in vitro interaction of the spike protein of the SARS-CoV-2 virus with various subunits of nAChRs. Electrophysiology recordings were conducted at \u03b14\u03b22, \u03b13\u03b24, \u03b13\u03b15\u03b24, \u03b14\u03b16\u03b22, and \u03b17 neuronal nAChRs expressed in Xenopus oocytes. In cells expressing the \u03b14\u03b22 or \u03b14\u03b16\u03b22 nAChRs, exposure to the 1 \u00b5g\/mL Spike-RBD protein caused a marked reduction of the current amplitude; effects at the \u03b13\u03b15\u03b24 receptor were equivocal and effects at the \u03b13\u03b24 and \u03b17 receptors were absent. Overall, the spike protein of the SARS-CoV-2 virus can interact with select nAChRs, namely the \u03b14\u03b22 and\/or \u03b14\u03b16\u03b22 subtypes, likely at an allosteric binding site. The nAChR agonist varenicline has the potential to interact with Spike-RBD and form a complex that may interfere with spike function, although this effect appears to have been lost with the omicron mutation. These results help understand nAChR\u2019s involvement with acute and long-term sequelae associated with COVID-19, especially within the central nervous system.<\/jats:p>","DOI":"10.3390\/ijms24065597","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T05:53:44Z","timestamp":1678859624000},"page":"5597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline"],"prefix":"10.3390","volume":"24","author":[{"given":"Eric C.","family":"Carlson","sequence":"first","affiliation":[{"name":"Oyster Point Pharma, Inc., Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Macsai","sequence":"additional","affiliation":[{"name":"Oyster Point Pharma, Inc., Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Bertrand","sequence":"additional","affiliation":[{"name":"HiQScreen S\u00e0rl, 1222 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Bertrand","sequence":"additional","affiliation":[{"name":"HiQScreen S\u00e0rl, 1222 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-3538","authenticated-orcid":false,"given":"Jeffrey","family":"Nau","sequence":"additional","affiliation":[{"name":"Oyster Point Pharma, Inc., Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rajpal, V.R., Sharma, S., Sehgal, D., Singh, A., Kumar, A., Vaishnavi, S., Tiwari, M., Bhalla, H., Goel, S., and Raina, S.N. 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