SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity.
J Mol Cell Biol
; 12(12): 916-932, 2020 10 12.
Article
in English
| MEDLINE | ID: covidwho-968717
ABSTRACT
There is a link between high lipopolysaccharide (LPS) levels in the blood and the metabolic syndrome, and metabolic syndrome predisposes patients to severe COVID-19. Here, we define an interaction between SARS-CoV-2 spike (S) protein and LPS, leading to aggravated inflammation in vitro and in vivo. Native gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to LPS. Microscale thermophoresis yielded a KD of â¼47 nM for the interaction. Computational modeling and all-atom molecular dynamics simulations further substantiated the experimental results, identifying a main LPS-binding site in SARS-CoV-2 S protein. S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells and cytokine responses in human blood and peripheral blood mononuclear cells, respectively. The in vitro inflammatory response was further validated by employing NF-κB reporter mice and in vivo bioimaging. Dynamic light scattering, transmission electron microscopy, and LPS-FITC analyses demonstrated that S protein modulated the aggregation state of LPS, providing a molecular explanation for the observed boosting effect. Taken together, our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Lipopolysaccharides
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Inflammation
Type of study:
Prognostic study
Topics:
Long Covid
Language:
English
Journal:
J Mol Cell Biol
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
Jmcb
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