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SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity.
Petruk, Ganna; Puthia, Manoj; Petrlova, Jitka; Samsudin, Firdaus; Strömdahl, Ann-Charlotte; Cerps, Samuel; Uller, Lena; Kjellström, Sven; Bond, Peter J; Schmidtchen, And Artur.
  • Petruk G; Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden.
  • Puthia M; Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden.
  • Petrlova J; Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden.
  • Samsudin F; Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore.
  • Strömdahl AC; Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden.
  • Cerps S; Unit of Respiratory Immunopharmacology, Department of Experimental Medicine, Lund University, SE-22184 Lund, Sweden.
  • Uller L; Unit of Respiratory Immunopharmacology, Department of Experimental Medicine, Lund University, SE-22184 Lund, Sweden.
  • Kjellström S; Division of Mass Spectrometry, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden.
  • Bond PJ; Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore.
  • Schmidtchen AA; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
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 ∼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.
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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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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