{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:11:14Z","timestamp":1792098674095,"version":"4.4.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017-02341"],"award-info":[{"award-number":["2017-02341"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Welander-Finsen, Crafoord, Torsten S\u00f6derberg, and \u00d6sterlund Foundations"},{"name":"The Royal Physiographic Society of Lund"},{"name":"The Swedish Government Funds for Clinical Research"},{"name":"BII"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u223c47\u2009nM 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-\u03baB) 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-\u03baB 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.<\/jats:p>","DOI":"10.1093\/jmcb\/mjaa067","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T08:02:34Z","timestamp":1606291354000},"page":"916-932","source":"Crossref","is-referenced-by-count":151,"title":["SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1336-2900","authenticated-orcid":false,"given":"Ganna","family":"Petruk","sequence":"first","affiliation":[{"name":"Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Puthia","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitka","family":"Petrlova","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdaus","family":"Samsudin","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Charlotte","family":"Str\u00f6mdahl","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Cerps","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Immunopharmacology, Department of Experimental Medicine, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Uller","sequence":"additional","affiliation":[{"name":"Unit of Respiratory Immunopharmacology, Department of Experimental Medicine, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Kjellstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Mass Spectrometry, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Bond","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore"},{"name":"Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9209-3141","authenticated-orcid":false,"given":"and Artur","family":"Schmidtchen","sequence":"additional","affiliation":[{"name":"Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden"},{"name":"Copenhagen Wound Healing Center, Bispebjerg Hospital, Department of Biomedical Sciences, University of Copenhagen, DK-2400 Copenhagen, Denmark"},{"name":"Dermatology, Sk\u00e5ne University Hospital, SE-22185 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"2021031110030747500_mjaa067-B1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"2021031110030747500_mjaa067-B2","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1177\/00220345950740040501","article-title":"Differential expression of IL-1\u03b2, TNF-\u03b1, IL-6, and IL-8 in human monocytes in response to lipopolysaccharides from different microbes","volume":"74","author":"Agarwal","year":"1995","journal-title":"J. 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