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The SARS-CoV2 envelope is distinct from host membranes, exposes pro-coagulant lipids, and can be inactivated in vivo by surfactant-containing oral rinses.
Zack Saud; Victoria J Tyrrell; Andreas Zaragkoulias; Majd B Protty; Evelina Statkute; Anzelika Rubina; Kirsten Bentley; Daniel A White; Patricia Dos Santos Rodrigues; Robert C Murphy; Harald Kofeler; William J Griffiths; Jorge Alvarez-Jarreta; Richard William Brown; Robert G Newcombe; James Heyman; Manon Pritchard; Robert WJ Mcleod; Arvind Arya; Ceri-Ann Lynch; David Owens; Vince Jenkins; Niklaas J Buurma; Valerie B O'Donnell; David W Thomas; Richard J Stanton.
Afiliação
  • Zack Saud; Cardiff University
  • Victoria J Tyrrell; Cardiff University
  • Andreas Zaragkoulias; Cardiff University
  • Majd B Protty; Cardiff University
  • Evelina Statkute; Cardiff University
  • Anzelika Rubina; Cardiff University
  • Kirsten Bentley; Cardiff University
  • Daniel A White; Cardiff University
  • Patricia Dos Santos Rodrigues; Cardiff University
  • Robert C Murphy; University of Colorado Denver
  • Harald Kofeler; Medical University of Graz
  • William J Griffiths; Swansea University
  • Jorge Alvarez-Jarreta; European Bioinformatics Institute
  • Richard William Brown; Cardiff and Vale University Health Board
  • Robert G Newcombe; Cardiff University
  • James Heyman; Cardiff and Vale University Health Board
  • Manon Pritchard; Cardiff University
  • Robert WJ Mcleod; Cardiff University
  • Arvind Arya; Betsi Cadwaladr University Health Board
  • Ceri-Ann Lynch; Cwm Taf University Health Board
  • David Owens; Cardiff and Vale University Health Board
  • Vince Jenkins; Cardiff and Vale University Health Board
  • Niklaas J Buurma; Cardiff University
  • Valerie B O'Donnell; Cardiff University
  • David W Thomas; Cardiff University
  • Richard J Stanton; Cardiff University
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22270842
ABSTRACT
The lipid envelope of SARS-CoV2 is an essential component of the virus, however its molecular composition is unknown. Addressing this knowledge gap could support the design of anti-viral agents, and further understanding of viral interaction with extracellular host proteins, infectivity, pathogenicity, and innate immune system clearance. Lipidomics analysis of SARS-CoV2 particles generated from Vero or A549 cells revealed that the virus envelope comprised mainly of phospholipids (PL), primarily phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), with very little cholesterol, sphingolipids or other lipids, indicating significant differences from host membranes. Unlike healthy cellular membranes, procoagulant aminoPL (aPL), specifically PE and phosphatidylserine (PS), were present on the external side at levels far exceeding those seen on activated platelets. As a result, purified virions directly promoted coagulation. To investigate whether these differences enabled the viral envelope to be selectively targeted at relevant sites in vivo, we tested whether non-toxic oral rinses containing lipid disrupting chemicals could reduce viral infectivity. Products containing PL-disrupting surfactant solutions (cetylpyridinium chloride (CPC) or ethyl lauroyl arginate) met EN14476 virucidal standards in vitro, however products containing essential oils, PVP-I, or Chlorhexidine did not, nor did rinses containing components that altered the critical micelle concentration of CPC. This result was recapitulated in vivo, where a 30-second oral rinse with CPC-mouthwash eliminated live virus in the oral cavity of COVID19 patients for at least 1hr, while PVP-Iodine and saline mouthwashes were ineffective. Thus, the SARS-CoV2 lipid envelope is distinct from the host plasma membrane which may enable design of selective anti-viral approaches, it exposes PE and PS which may influence thrombosis, pathogenicity, and inflammation, and can be selectively targeted in vivo by specific oral rinses.
Licença
cc_by_nc_nd
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Idioma: Inglês Ano de publicação: 2022 Tipo de documento: Preprint
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