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| 1 | SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity显示文摘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 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-k B)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-kB 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. | Ganna Petruk Manoj Puthia Jitka Petrlova Firdaus Samsudin Ann-Charlotte Stromdahl Samuel Cerps Lena Uller Sven Kjellstrom Peter J.Bond Artur Schmidtchen | 2020 | Journal of Molecular Cell Biology2020，12，12： | 3 |
| 2 | Contributions of evaporation, isotopic non‐steady state transpiration and atmospheric mixing on the δ<sup>18</sup>O of water vapour in Pacific Northwest coniferous forests显示文摘 | CHUN‐TALAI JAMES R.EHLERINGER BARBARA J.BOND KYAW THAPAW U | 2005 | Plant Cell & Environment2005，，1： | 1 |
| 3 | Interpreting diel hysteresis between soil respiration and temperature显示文摘 | CLAIRE L.PHILLIPS NICKNICKERSON DAVIDRISK BARBARA J.BOND | 2010 | Global Change Biology2010，，1： | 1 |
| 4 | SARS-CoV-2 spike protein as a bacterial lipopolysaccharide delivery system in an overzealous inflammatory cascade显示文摘Accumulating evidence indicates a potential role for bacterial lipopolysaccharide(LPs)in the overactivation of the immune response during SARS-CoV-2 infection.LPS is recognized by Toll-like receptor 4,mediating proinflammatory effects.We previously reported that LPS directly interacts with SARS-CoV-2 spike(S)protein and enhances proinflammatory activities.Using native gel electrophoresis and hydrogen-deuterium exchange mass spectrometry,we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the S protein.Molecular simulations validated by a microscale thermophoresis binding assay revealed that LPS binds to the S2 pocket with a lower affinity compared to S1,suggesting a role as an intermediate in LPS transfer.Congruently,nuclear factor-kappa B(NF-kB)activation in monocytic THP-1 cells is strongly boosted by S2.Using NF-kB reporter mice followed by bioimaging,a boosting effect was observed for both S1 and S2,with the former potentially facilitated by proteolysis.The Omicron S variant binds to LPS,but with reduced affinity and LPS boosting in vitro and in vivo.Taken together,the data provide a molecular mechanism by which S protein augments LPS-mediated hyperinflammation. | Firdaus Samsudin Palur Raghuvamsi Ganna Petruk Manoj Puthia Jitka Petrlova Paul MacAry Ganesh S.Anand Peter J.Bond Artur Schmidtchen | 2022 | Journal of Molecular Cell Biology2022，14，9： | 0 |
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