Publication date: Jul 29, 2024
Currently, pathophysiological mechanisms of post-acute sequelae of coronavirus disease-19-cardiovascular syndrome (PASC-CVS) remain unknown. 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- and β-AR, but not to D1-dopamine receptor. These interactions were blocked by β- and β-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. 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.
| Concepts | Keywords |
|---|---|
| Cardiac | agonist |
| Coronavirus | cardiac sympathetic hyperactivity |
| Genes | long COVID |
| Microscale | β‐adrenergic receptor |
| Mutants |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | sequelae |
| disease | MESH | long COVID |
| disease | MESH | coronavirus disease-19 |
| disease | MESH | syndrome |
| disease | MESH | severe acute respiratory syndrome |
| disease | VO | frequency |
| disease | IDO | assay |
| drug | DRUGBANK | Dopamine |
| disease | VO | dose |
| drug | DRUGBANK | Cyclic Adenosine Monophosphate |
| disease | IDO | production |
| drug | DRUGBANK | Epinephrine |