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HGNC Genes

SARS-CoV-2 proteins

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

    Authors: Ganna Petruk; Manoj Puthia; Jitka Petrlova; Ann-Charlotte Strömdahl; Sven Kjellström; Artur Schmidtchen

    doi:10.1101/2020.06.29.175844 Date: 2020-06-29 Source: bioRxiv

    ABSTRACTThere is a well-known and established link between high lipopolysaccharide ( LPS HGNC) levels in blood and the metabolic syndrome MESHD ( MS MESHD). MS MESHD is a risk factor for developing severe COVID-19 MESHD and acute respiratory distress syndrome MESHD ( ARDS MESHD). Here we define an interaction between SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD ( S) protein PROTEIN and LPS HGNC and its link to aggravated inflammation MESHD in vitro and in vivo. Electrophoresis under native conditions demonstrated that SARS-CoV-2 S MESHD S protein PROTEIN binds to Escherichia coli LPS HGNC, forming high molecular weight aggregates. Microscale thermophoresis analysis further defined the interaction, having a KD of ~47 nM, similar to the observed affinity between LPS HGNC and the human receptor CD14 HGNC. Moreover, S protein PROTEIN, when combined with low levels of LPS HGNC, boosted nuclear factor-kappa B (NF-κB) and cytokine responses in monocytic THP-1 cells and human blood, respectively. In an experimental model of localized inflammation MESHD, employing NF-κB reporter mice and in vivo bioimaging, S protein PROTEIN in conjunction with LPS significantly increased the inflammatory response when compared with S protein PROTEIN and LPS alone. Apart from providing information on LPS HGNC as a ligand for S protein PROTEIN, our results are of relevance for studies on comorbidities involving bacterial endotoxins, such as the MS MESHD, or co-existing acute and chronic infections MESHD in COVID-19 MESHD patients.Competing Interest StatementA.S is a founder and shareholder of in2cure AB, a company developing therapies based on host defense peptides. A patent application related to the present work, with A.S. and G.P. listed as inventors, has been filed.AbbreviationsARDSacute respiratory distress syndromeCOVID-19coronavirus disease 2019MSmetabolic syndromeLBPLPS MESHD COVID-19 MESHD coronavirus disease 2019 MESHDMSmetabolic syndromeLBPLPS-binding proteinLPSlipopolysaccharideNF-κBnuclear factor-kappa BSARS-CoV-2 Spike proteinS PROTEIN proteinTLR4Toll-like receptor 4View Full Text

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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