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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 | Blastocystis ratti induces contact- independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells显示文摘 | Puthia MK Sio SW Lu J | 2006 | Infect Immun2006，74，7： | 1 |
| 3 | The Humoral Pattern Recognition Molecule PTX3 Is a Key Component of Innate Immunity against Urinary Tract Infection显示文摘 | Sébastien Jaillon Federica Moalli Bryndis Ragnarsdottir Eduardo Bonavita Manoj Puthia Federica Riva Elisa Barbati Manuela Nebuloni Lidija Cvetko Krajinovic Alemka Markotic Sonia Valentino Andrea Doni Silvia Tartari Giorgio Graziani Alessandro Montanelli Y | 2014 | Immunity2014，，4： | 1 |
| 4 | The neuropeptide substance P is a critical mediator of burn - induced acute lung injury显示文摘 | Sio SW Puthia MK Lu J | 2008 | J Immunol2008，180，12： | 1 |
| 5 | The neuropeptide substance P is a critical mediator of burn - induced acute lung injury 显示文摘 | Sio SW Puthia MK Lu J | 2008 | J Immunol2008，180，12： | 1 |
| 6 | The neuropeptide substance P is a critical mediator of burn-induced acute lung injury显示文摘 | Sio SW Puthia MK Lu J | 2008 | J Immunol2008，180，12： | 1 |
| 7 | 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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