SARS-CoV-2 spike protein aggregation is triggered by bacterial lipopolysaccharide

FEBS Letters

article

Jitka Petrlova¹  Firdaus Samsudin²  Peter J. Bond²  Artur Schmidtchen¹ 

[1] Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University;Bioinformatics Institute ,(BII), Agency for Science, Technology and Research;Department of Biological Sciences, National University of Singapore;Department of Biomedical Sciences, Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen;Dermatology, Skåne University Hospital

关键词: COVID-19;    endotoxins;    inflammation;    lipopolysaccharide;    protein-aggregation;    spike protein;   

DOI  :  10.1002/1873-3468.14490

来源: John Wiley & Sons Ltd.

【 摘 要 】

SARS-CoV-2 spike (S) protein is crucial for virus invasion in COVID-19. Here, we showed that lipopolysaccharide (LPS) can trigger S protein aggregation at high doses of LPS and S protein. We demonstrated the formation of S protein aggregates by microscopy analyses, aggregation and gel shift assays. LPS at high levels boosts the formation of S protein aggregates as detected by amytracker and thioflavin T dyes that specifically bind to aggregating proteins. We validated the role of LPS by blocking the formation of aggregates by the endotoxin-scavenging thrombin-derived peptide TCP-25. Aggregation-prone sequences in S protein are predicted to be nearby LPS binding sites, while molecular simulations showed stable formation of S protein–LPS higher-order oligomers. Collectively, our results provide evidence of LPS-induced S protein aggregation.

【 授权许可】

Unknown