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

Petrlova, JitkaLund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Schmidtchen lab,Forskargrupper vid Lunds universitet,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Schmidtchen Lab,Lund University Research Groups,Division of Dermatology and Venereology, Department of Clinical Sciences Lund University Sweden (author)

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.

Samsudin, FirdausBioinformatics Institute (BII) Agency for Science, Technology and Research (A*STAR) Singapore City Singapore (author)
Bond, Peter J.Bioinformatics Institute (BII) Agency for Science, Technology and Research (A*STAR) Singapore City Singapore;Department of Biological Sciences National University of Singapore Singapore,National University of Singapore (author)
Schmidtchen, ArturLund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups,Division of Dermatology and Venereology, Department of Clinical Sciences Lund University Sweden;Department of Biomedical Sciences, Copenhagen Wound Healing Center, Bispebjerg Hospital University of Copenhagen Denmark;Dermatology Skåne University Hospital Lund Sweden,Skåne University Hospital(Swepub:lu)derm-asc (author)
Dermatologi och venereologi, LundSektion III (creator_code:org_t)

By the author/editor: Petrlova, Jitka; Samsudin, Firdau ...; Bond, Peter J.; Schmidtchen, Art ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

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