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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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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa60471
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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.
College: Swansea University Medical School
Funders: 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).
Issue: 6
Start Page: 100208