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The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses

Zack Saud, Victoria J. Tyrrell, Andreas Zaragkoulias Orcid Logo, Majd B. Protty Orcid Logo, Evelina Statkute, Anzelika Rubina, Kirsten Bentley Orcid Logo, Daniel A. White, Patricia Dos Santos Rodrigues Orcid Logo, Robert C. Murphy, Harald Köfeler, William Griffiths Orcid Logo, Jorge Alvarez-Jarreta Orcid Logo, Richard William Brown Orcid Logo, Robert G. Newcombe, James Heyman, Manon Pritchard, Robert WJ. Mcleod Orcid Logo, Arvind Arya, Ceri-Ann Lynch, David Owens, P Vince Jenkins, Niklaas J. Buurma Orcid Logo, Valerie B. O’Donnell, David W. Thomas Orcid Logo, Richard J. Stanton Orcid Logo

Journal of Lipid Research, Volume: 63, Issue: 6, Start page: 100208

Swansea University Author: William Griffiths Orcid Logo

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DOI (Published version): 10.1016/j.jlr.2022.100208

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...

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Published in: Journal of Lipid Research
ISSN: 0022-2275
Published: Elsevier BV 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa60471
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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.</abstract><type>Journal Article</type><journal>Journal of Lipid Research</journal><volume>63</volume><journalNumber>6</journalNumber><paginationStart>100208</paginationStart><paginationEnd/><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0022-2275</issnPrint><issnElectronic/><keywords/><publishedDay>1</publishedDay><publishedMonth>6</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-06-01</publishedDate><doi>10.1016/j.jlr.2022.100208</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>External research funder(s) paid the OA fee (includes OA grants disbursed by the Library)</apcterm><funders>R. 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spelling 2022-10-27T11:01:34.0261650 v2 60471 2022-07-13 The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2022-07-13 BMS 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. Journal Article Journal of Lipid Research 63 6 100208 Elsevier BV 0022-2275 1 6 2022 2022-06-01 10.1016/j.jlr.2022.100208 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) R. J. S. was partly funded by UK Research and Innovation/National Institute of Health Research through the UK Coronavirus Immunology Consortium. V. J. T., D. W., M. P., and P. D. S. R. are supported in part by the Welsh Government/EU Ser Cymru Programme. M. B. P. was funded by a Wellcome Trust GW4CAT Training Fellowship (grant no.: 216278/Z/19/Z), and R. M. and M. J. P. are Welsh Clinical Academic Training Fellows. V. O. D. was a Royal Society Wolfson Merit Award Holder. A. Z. was funded by the Biotechnology and Biological Sciences Research Council (grant no.: BB/W003376/1). 2022-10-27T11:01:34.0261650 2022-07-13T09:12:05.7068747 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Zack Saud 1 Victoria J. Tyrrell 2 Andreas Zaragkoulias 0000-0002-2290-0128 3 Majd B. Protty 0000-0001-8992-9120 4 Evelina Statkute 5 Anzelika Rubina 6 Kirsten Bentley 0000-0002-6619-2098 7 Daniel A. White 8 Patricia Dos Santos Rodrigues 0000-0003-0768-0013 9 Robert C. Murphy 10 Harald Köfeler 11 William Griffiths 0000-0002-4129-6616 12 Jorge Alvarez-Jarreta 0000-0002-0946-0957 13 Richard William Brown 0000-0001-8182-7314 14 Robert G. Newcombe 15 James Heyman 16 Manon Pritchard 17 Robert WJ. Mcleod 0000-0003-3221-6896 18 Arvind Arya 19 Ceri-Ann Lynch 20 David Owens 21 P Vince Jenkins 22 Niklaas J. Buurma 0000-0003-0260-5057 23 Valerie B. O’Donnell 24 David W. Thomas 0000-0001-7319-5820 25 Richard J. Stanton 0000-0002-6799-1182 26 60471__24729__202a7b9b329747a0ba917f9fe5ed145c.pdf Saud JLR 2022.pdf 2022-07-25T11:26:24.1343097 Output 1708045 application/pdf Version of Record true © 2022 THE AUTHORS. This is an open access article under the CC BY license true eng http://creativecommons.org/licenses/by/4.0/
title The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
spellingShingle The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
William Griffiths
title_short The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
title_full The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
title_fullStr The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
title_full_unstemmed The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
title_sort The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_William Griffiths
author William Griffiths
author2 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 Griffiths
Jorge Alvarez-Jarreta
Richard William Brown
Robert G. Newcombe
James Heyman
Manon Pritchard
Robert WJ. Mcleod
Arvind Arya
Ceri-Ann Lynch
David Owens
P Vince Jenkins
Niklaas J. Buurma
Valerie B. O’Donnell
David W. Thomas
Richard J. Stanton
format Journal article
container_title Journal of Lipid Research
container_volume 63
container_issue 6
container_start_page 100208
publishDate 2022
institution Swansea University
issn 0022-2275
doi_str_mv 10.1016/j.jlr.2022.100208
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description 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.
published_date 2022-06-01T04:18:36Z
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score 10.999524

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