SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

Ganna Petruk, Manoj Puthia, Jitka Petrlova, Firdaus Samsudin, Ann-Charlotte Strömdahl, Samuel Cerps, Lena Uller, Sven Kjellström, Peter John Bond, Artur Schmidtchen

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)916–932
JournalJournal of Molecular Cell Biology
Issue number12
Publication statusPublished - 2020

Subject classification (UKÄ)

  • Cell and Molecular Biology


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