ArticleProceedings of the National Academy of Sciences of the United States of America2022
An experimental test of the nicotinic hypothesis of COVID-19.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Peptides containing SARS-CoV-2 spike-protein residues are antagonists of α7 and α9α10 nAChRs and modulate interleukin-1β release from human monocytic THP-1 cells.The Journal of biological chemistry · 2026Article
- HSV1 glycoprotein D utilizes an LY6-like binding domain to inhibit alpha7 nicotinic receptors.Npj viruses · 2025Article
- Long COVID - a critical disruption of cholinergic neurotransmission?Bioelectronic medicine · 2025Review
- Design, Synthesis, and Structure-Activity Relationships of Novel Peptide Derivatives of the Severe Acute Respiratory Syndrome-Coronavirus-2 Spike-Protein that Potently Inhibit Nicotinic Acetylcholine Receptors.Journal of medicinal chemistry · 2024Article
- SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors.The Journal of biological chemistry · 2023Article
- α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain.International journal of molecular sciences · 2023Review
- The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline.International journal of molecular sciences · 2023Article
- Nicotine exposure decreases likelihood of SARS-CoV-2 RNA expression and neuropathology in the hACE2 mouse brain but not moribundity.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The pathophysiological mechanisms underlying the constellation of symptoms that characterize COVID-19 are only incompletely understood. In an effort to fill these gaps, a "nicotinic hypothesis," which posits that nicotinic acetylcholine receptors (AChRs) act as additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptors, has recently been put forth. A key feature of the proposal (with potential clinical ramifications) is the suggested competition between the virus' spike protein and small-molecule cholinergic ligands for the receptor's orthosteric binding sites. This notion is reminiscent of the well-established role of the muscle AChR during rabies virus infection. To address this hypothesis directly, we performed equilibrium-type ligand-binding competition assays using the homomeric human α7-AChR (expressed on intact cells) as the receptor, and radio-labeled α-bungarotoxin (α-BgTx) as the orthosteric-site competing ligand. We tested different SARS-CoV-2 spike protein peptides, the S1 domain, and the entire S1-S2 ectodomain, and found that none of them appreciably outcompete [
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.