The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline
Abstract
:1. Introduction
2. Results
2.1. Spike-RBD Interacts with the Human α4β2 and α4α6β2 nAChRs and Possibly the α3α5β4 nAChR, but Not the α3β4 and α7 nAChRs
2.2. The S2 Subunit of the S Protein Interacts with the Human α4β2 nAChR, but Not the α4α6β2, α3β4, and α3α5β4 nAChRs
2.3. The S1 Subunit of the S Protein Interacts with the Human α4β2 nAChRs at an Allosteric Binding Site That Inhibits Receptor Activity
2.4. The SARS-CoV-2 B.1.1.529 Spike-RBD Protein Interacts with the Human α4β2 nAChR at an Allosteric Binding Site That Potentiates Receptor Activity
2.5. Preincubation of Varenicline with Spike-RBD Indicates That Varenicline Inhibition of the Human α4β2 nAChR Is Modified by Spike-RBD
2.6. The SARS-CoV-2 B.A.1 (Omicron) Spike-RBD Protein Interacts with the Human α4β2 nAChRs at an Allosteric Binding Site That Potentiates Receptor Activity
3. Discussion
4. Materials and Methods
4.1. Human nAChRs
4.2. SARS-CoV-2 S Protein
4.3. Varenicline Tartrate
4.4. Electrophysiological Recordings
4.5. SARS-CoV-2 B.1.1.7 S Protein Interaction with Human nAChR Subtypes
4.6. SARS-CoV-2 B.1.1.529 (Omicron Variant) S Protein Interaction with Human α4β2 nAChRs
4.7. Varenicline Interaction with Spike-RBD and SARS-CoV-2 B.1.1.529 Spike-RBD
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Carlson, E.C.; Macsai, M.; Bertrand, S.; Bertrand, D.; Nau, J. The SARS-CoV-2 Virus and the Cholinergic System: Spike Protein Interaction with Human Nicotinic Acetylcholine Receptors and the Nicotinic Agonist Varenicline. Int. J. Mol. Sci. 2023, 24, 5597. https://doi.org/10.3390/ijms24065597
Carlson EC, Macsai M, Bertrand S, Bertrand D, Nau J. 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. 2023; 24(6):5597. https://doi.org/10.3390/ijms24065597
Chicago/Turabian StyleCarlson, Eric C., Marian Macsai, Sonia Bertrand, Daniel Bertrand, and Jeffrey Nau. 2023. "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 24, no. 6: 5597. https://doi.org/10.3390/ijms24065597