SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity. (9th December 2020)

• Record Type: Journal Article
• Authors: Petruk, Ganna; Puthia, Manoj; Petrlova, Jitka; Samsudin, Firdaus; Strömdahl, Ann-Charlotte; Cerps, Samuel; Uller, Lena; Kjellström, Sven; Bond, Peter J; Schmidtchen, and Artur
• Editors: Su, Bing
• Is Part Of: Journal of molecular cell biology. Volume 12:Number 12(2020)
• Page Start: 916
• Page End: 932
• Publication Date: 2020-12-09
• Subjects: COVID-19 -- SARS-CoV-2 -- spike protein -- lipopolysaccharide -- inflammation -- aggregation -- metabolic syndrome; Molecular biology -- Periodicals; 571.605
• DOI: 10.1093/jmcb/mjaa067
• Languages: English
• ISSNs: 1674-2788

Abstract

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 K D of ∼47 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.