PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Molecular Modelling and Docking Experiments Examining the Interaction between SARS-CoV-2 Spike Glycoprotein and Neuronal Nicotinic Acetylcholine Receptors
Farsalinos, K.; Eliopoulos, E.; Leonidas, D.; Papadopoulos, G.; Tzartos, S.; Poulas, K. Molecular Modelling and Docking Experiments Examining the Interaction between SARS-CoV-2 Spike Glycoprotein and Neuronal Nicotinic Acetylcholine Receptors. Preprints2020, 2020050365. https://doi.org/10.20944/preprints202005.0365.v1
APA Style
Farsalinos, K., Eliopoulos, E., Leonidas, D., Papadopoulos, G., Tzartos, S., & Poulas, K. (2020). Molecular Modelling and Docking Experiments Examining the Interaction between SARS-CoV-2 Spike Glycoprotein and Neuronal Nicotinic Acetylcholine Receptors. Preprints. https://doi.org/10.20944/preprints202005.0365.v1
Chicago/Turabian Style
Farsalinos, K., Socrates Tzartos and Konstantinos Poulas. 2020 "Molecular Modelling and Docking Experiments Examining the Interaction between SARS-CoV-2 Spike Glycoprotein and Neuronal Nicotinic Acetylcholine Receptors" Preprints. https://doi.org/10.20944/preprints202005.0365.v1
Abstract
While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine for other potential interactions between the virus and other cell receptors. Based on the clinical observation of low smoking prevalence among hospitalized COVID-19 patients, we recently identified a “toxin-like” amino acid (aa) sequence on the receptor binding domain of the spike glycoprotein of SARS-CoV-2 (aa 375-390) with homology to a sequence of a snake venom toxin, which could interact with nicotinic acetylcholine receptors (nAChRs). We now present computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 spike glycoprotein and the extracellular domain of the nAChR alpha9 subunit. We identified an interaction between the aa381-386 of the SARS-CoV-2 spike glycoprotein and the aa189-192 of the extracellular domain of the nAChR alpha9 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 alpha9 nAChR and alpha-bungarotoxin. A similar interaction was observed between the pentameric alpha7 AChR and the SARS-CoV-2 spike glycoprotein. Our findings support the hypothesis that severe COVID-19 may be associated with disruption of the nicotinic cholinergic system which could be caused by an interaction between SARS-CoV-2 and nAChRs.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
