The SARS-CoV2 envelope differs from host cells,exposes procoagulant lipids,and is disrupted in vivo by oral rinses |
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Authors: | 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 Köfeler William J. Griffiths Jorge Alvarez-Jarreta Richard William Brown Robert G. Newcombe James Heyman Manon Pritchard Robert WJ. Mcleod Richard J. Stanton |
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Affiliation: | 1. Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom;2. Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA;3. Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria;4. Medical School, Swansea University, Swansea, United Kingdom;5. ENT Department, Betsi Cadwaladr University Health Board, Wrexham Maelor Hospital, Wrexham, United Kingdom;6. Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom;7. Division of Surgery, Cardiff and Vale University Health Board, Cardiff, United Kingdom;8. Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, United Kingdom;9. Anaesthetics and Critical Care Directorate, Cwm Taf University Health Board, Royal Glamorgan Hospital, Llantrisant, United Kingdom;10. Haemostasis Diagnosis and Research, University Hospital Wales, Cardiff, United Kingdom;11. Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Cardiff, United Kingdom |
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Abstract: | The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses. |
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Keywords: | phospholipids lipidomics inflammation virology clinical trials aminophospholipids coagulation mouthwash cetylpyridinium chloride CPC ACE2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" angiotensin-converting enzyme 2 aPL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" aminophospholipid CE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" cholesteryl ester Cer" },{" #name" :" keyword" ," $" :{" id" :" kwrd0095" }," $$" :[{" #name" :" text" ," _" :" ceramide cmc" },{" #name" :" keyword" ," $" :{" id" :" kwrd0105" }," $$" :[{" #name" :" text" ," _" :" critical micelle concentration COVID-19" },{" #name" :" keyword" ," $" :{" id" :" kwrd0115" }," $$" :[{" #name" :" text" ," _" :" coronavirus disease 2019 CPC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0125" }," $$" :[{" #name" :" text" ," _" :" cetylpyridinium chloride CUR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0135" }," $$" :[{" #name" :" text" ," _" :" curtain gas DHCer" },{" #name" :" keyword" ," $" :{" id" :" kwrd0145" }," $$" :[{" #name" :" text" ," _" :" dihydroceramide ER" },{" #name" :" keyword" ," $" :{" id" :" kwrd0155" }," $$" :[{" #name" :" text" ," _" :" endoplasmic reticulum GS1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0165" }," $$" :[{" #name" :" text" ," _" :" source gas 1 GS2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0175" }," $$" :[{" #name" :" text" ," _" :" source gas 2 HILIC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0185" }," $$" :[{" #name" :" text" ," _" :" hydrophilic interaction liquid chromatography HSV" },{" #name" :" keyword" ," $" :{" id" :" kwrd0195" }," $$" :[{" #name" :" text" ," _" :" herpes simplex virus IPM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0205" }," $$" :[{" #name" :" text" ," _" :" isopropyl myristate IS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0215" }," $$" :[{" #name" :" text" ," _" :" ionization voltage LAE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0225" }," $$" :[{" #name" :" text" ," _" :" ethyl lauroyl arginate LMSD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0235" }," $$" :[{" #name" :" text" ," _" :" LIPID MAPS Structure Database MRM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0245" }," $$" :[{" #name" :" text" ," _" :" multiple reaction monitoring PC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0255" }," $$" :[{" #name" :" text" ," _" :" phosphatidylcholine PE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0265" }," $$" :[{" #name" :" text" ," _" :" phosphatidylethanolamine PFU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0275" }," $$" :[{" #name" :" text" ," _" :" plaque-forming unit PG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0285" }," $$" :[{" #name" :" text" ," _" :" phosphatidylglycerol PI" },{" #name" :" keyword" ," $" :{" id" :" kwrd0295" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol PL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0305" }," $$" :[{" #name" :" text" ," _" :" phospholipid PS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0315" }," $$" :[{" #name" :" text" ," _" :" phosphatidylserine PVP-I" },{" #name" :" keyword" ," $" :{" id" :" kwrd0325" }," $$" :[{" #name" :" text" ," _" :" povidone-iodine SARS-CoV2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0335" }," $$" :[{" #name" :" text" ," _" :" severe acute respiratory syndrome coronavirus 2 SEC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0345" }," $$" :[{" #name" :" text" ," _" :" size-exclusion chromatography SL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0355" }," $$" :[{" #name" :" text" ," _" :" sphingolipid TAG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0365" }," $$" :[{" #name" :" text" ," _" :" triacylglyceride TEM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0375" }," $$" :[{" #name" :" text" ," _" :" temperature TG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0385" }," $$" :[{" #name" :" text" ," _" :" triglyceride TMPRSS2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0395" }," $$" :[{" #name" :" text" ," _" :" transmembrane serine protease 2 |
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