ArticleInternational journal of molecular sciences2020
Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication.Harm reduction journal · 2021Pooled it
- 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
- Assessment of smoking exposure by urine cotinine levels in severe COVID-19 patients: a case-control study.Scientific reports · 2025Observational
- Double-seropositive Myasthenia Gravis Following COVID-19.Internal medicine (Tokyo, Japan) · 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
- The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank.Nutrients · 2024Article
- Review
- Substances of abuse and their effect on SAR-CoV-2 pathogenesis.NeuroImmune pharmacology and therapeutics · 2023Review
- COVID-19 and tobacco products use among US adults, 2021 National Health Interview Survey.Health science reports · 2023Article
- The controversial effect of smoking and nicotine in SARS-CoV-2 infection.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Review
- 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
- Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration?Bioelectronic medicine · 2023Article
- Potential value of neuroimmunotherapy for COVID-19: efficacies and mechanisms of vagus nerve stimulation, electroacupuncture, and cholinergic drugs.Frontiers in immunology · 2023Review
- An experimental test of the nicotinic hypothesis of COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Immunization with 674-685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice.Biochemical and biophysical research communications · 2022Article
- Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19.Free radical biology & medicine · 2022Review
- Tobacco product use and the risks of SARS-CoV-2 infection and COVID-19: current understanding and recommendations for future research.The Lancet. Respiratory medicine · 2022Review
- The association between tobacco use and COVID-19 in Qatar.Preventive medicine reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
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