1. SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID.
- Author
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Deng X, Cui H, Liang H, Wang X, Yu H, Wang J, Wang W, Liu D, Zhang Y, Dong E, Tang Y, and Xiao H
- Subjects
- Humans, Male, Female, Middle Aged, Post-Acute COVID-19 Syndrome, Aged, Molecular Docking Simulation, Myocytes, Cardiac metabolism, Myocytes, Cardiac drug effects, Adrenergic beta-Agonists pharmacology, Adrenergic beta-Agonists therapeutic use, Spike Glycoprotein, Coronavirus metabolism, COVID-19 complications, COVID-19 metabolism, SARS-CoV-2
- Abstract
Background: Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown., Methods and Results: Patients with PASC-CVS exhibited significantly higher circulating levels of severe acute respiratory syndrome-coronavirus-2 spike protein S1 than the non-PASC-CVS patients and healthy controls. Moreover, individuals with high plasma spike protein S1 concentrations exhibited elevated heart rates and normalized low frequency, suggesting cardiac β-adrenergic receptor (β-AR) hyperactivity. Microscale thermophoresis (MST) assay revealed that the spike protein bound to β
1 - and β2 -AR, but not to D1-dopamine receptor. These interactions were blocked by β1 - and β2 -AR blockers. Molecular docking and MST assay of β-AR mutants revealed that the spike protein interacted with the extracellular loop 2 of both β-ARs. In cardiomyocytes, spike protein dose-dependently increased the cyclic adenosine monophosphate production with or without epinephrine, indicating its allosteric effects on β-ARs., Conclusion: Severe acute respiratory syndrome-coronavirus-2 spike proteins act as an allosteric β-AR agonist, leading to cardiac β-AR hyperactivity, thus contributing to PASC-CVS., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)- Published
- 2024
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