2. Academic Validation
  3. SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID

SARS-CoV-2 spike protein acts as a β-adrenergic receptor agonist: A potential mechanism for cardiac sequelae of long COVID

  • J Intern Med. 2024 Sep;296(3):291-297. doi: 10.1111/joim.20000.
Xiangning Deng 1 2 3 4 5,  Hongtu Cui 1 2 3 4 5,  Hao Liang 6,  Xinyu Wang 1 2 3 4 5,  Haiyi Yu 1 2 3 4 5,  Jingjia Wang 1 2 3 4 5,  Wenyao Wang 1 2 3 4 5,  Dongyang Liu 5 6,  Youyi Zhang 1 2 3 4 5,  Erdan Dong 1 2 3 4 7,  Yida Tang 1 2 3 4 5,  Han Xiao 1 2 3 4 5 7 8
Affiliations

Affiliations

  • 1 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
  • 2 State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
  • 3 Haihe Laboratory of Cell Ecosystem, Beijing, China.
  • 4 Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China.
  • 5 Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China.
  • 6 Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
  • 7 University of Health and Rehabilitation Sciences, Qingdao, China.
  • 8 Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, China.
PMID: 39073192 DOI: 10.1111/joim.20000
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 β1- 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.

Keywords

SARS‐CoV‐2 spike protein; agonist; cardiac sympathetic hyperactivity; long COVID; β‐adrenergic receptor.

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