tetano
Editor, Senior Moderator
J Intern Med
. 2024 Jul 29.
doi: 10.1111/joim.20000. Online ahead of print. SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID
Xiangning Deng[SUP] 1 2 3 4 5 [/SUP], Hongtu Cui[SUP] 1 2 3 4 5 [/SUP], Hao Liang[SUP] 6 [/SUP], Xinyu Wang[SUP] 1 2 3 4 5 [/SUP], Haiyi Yu[SUP] 1 2 3 4 5 [/SUP], Jingjia Wang[SUP] 1 2 3 4 5 [/SUP], Wenyao Wang[SUP] 1 2 3 4 5 [/SUP], Dongyang Liu[SUP] 5 6 [/SUP], Youyi Zhang[SUP] 1 2 3 4 5 [/SUP], Erdan Dong[SUP] 1 2 3 4 7 [/SUP], Yida Tang[SUP] 1 2 3 4 5 [/SUP], Han Xiao[SUP] 1 2 3 4 5 7 8 [/SUP]
Affiliations
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[SUB]1[/SUB]- and β[SUB]2[/SUB]-AR, but not to D1-dopamine receptor. These interactions were blocked by β[SUB]1[/SUB]- and β[SUB]2[/SUB]-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.
Keywords: SARS‐CoV‐2 spike protein; agonist; cardiac sympathetic hyperactivity; long COVID; β‐adrenergic receptor.
. 2024 Jul 29.
doi: 10.1111/joim.20000. Online ahead of print. SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID
Xiangning Deng[SUP] 1 2 3 4 5 [/SUP], Hongtu Cui[SUP] 1 2 3 4 5 [/SUP], Hao Liang[SUP] 6 [/SUP], Xinyu Wang[SUP] 1 2 3 4 5 [/SUP], Haiyi Yu[SUP] 1 2 3 4 5 [/SUP], Jingjia Wang[SUP] 1 2 3 4 5 [/SUP], Wenyao Wang[SUP] 1 2 3 4 5 [/SUP], Dongyang Liu[SUP] 5 6 [/SUP], Youyi Zhang[SUP] 1 2 3 4 5 [/SUP], Erdan Dong[SUP] 1 2 3 4 7 [/SUP], Yida Tang[SUP] 1 2 3 4 5 [/SUP], Han Xiao[SUP] 1 2 3 4 5 7 8 [/SUP]
Affiliations
- PMID: 39073192
- DOI: 10.1111/joim.20000
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[SUB]1[/SUB]- and β[SUB]2[/SUB]-AR, but not to D1-dopamine receptor. These interactions were blocked by β[SUB]1[/SUB]- and β[SUB]2[/SUB]-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.
Keywords: SARS‐CoV‐2 spike protein; agonist; cardiac sympathetic hyperactivity; long COVID; β‐adrenergic receptor.