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

Saud, Zack, Tyrrell, Victoria J., Zaragkoulias, Andreas, Protty, Majd B., Statkute, Evelina, Rubina, Anzelika, Bentley, Kirsten ORCID: https://orcid.org/0000-0002-6619-2098, White, Daniel A., Dos Santos Rodrigues, Patricia, Murphy, Robert C., Köfeler, Harald, Griffiths, William J., Alvarez-Jarreta, Jorge, Brown, Richard William, Newcombe, Robert G. ORCID: https://orcid.org/0000-0003-4400-8867, Heyman, James, Pritchard, Manon ORCID: https://orcid.org/0000-0002-5135-4744, Mcleod, Robert W. J., Arya, Arvind, Lynch, Ceri-Ann, Owens, David, Jenkins, P. Vince, Buurma, Niklaas J. ORCID: https://orcid.org/0000-0003-0260-5057, O'Donnell, Valerie B. ORCID: https://orcid.org/0000-0003-4089-8460, Thomas, David W. ORCID: https://orcid.org/0000-0001-7319-5820 and Stanton, Richard J. ORCID: https://orcid.org/0000-0002-6799-1182 2022. The SARS-CoV2 envelope differs from host cells, exposes pro-coagulant lipids, and is disrupted in vivo by oral rinses. Journal of Lipid Research 63 (6) , 100208. 10.1016/j.jlr.2022.100208

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Abstract

The lipid envelope of 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 anti-viral agents, as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Using lipidomics analyses, we revealed that the virus envelope comprised mainly phospholipids (PL), with little cholesterol or sphingolipids, indicating significant differences from the composition of host membranes. Unlike cellular membranes, procoagulant aminophospholipids were present on the external side of the viral envelope at levels exceeding those on activated platelets. As a result, 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 viral infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride (CPC)) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, PVP-I, or Chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-second oral rinse with CPC mouthwash eliminated live virus in the oral cavity of COVID-19 patients for at least one hour, while PVP-Iodine and saline mouthwashes were found ineffective. We conclude the SARS-CoV-2 lipid envelope (i) is distinct from the host plasma membrane, which may enable design of selective anti-viral approaches; (ii) contains exposed PE and PS, which may influence thrombosis, pathogenicity, and inflammation; and (iii) can be selectively targeted in vivo by specific oral rinses.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry Dentistry Medicine Systems Immunity Research Institute (SIURI)
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0022-2275
Funders:	BBSRC
Date of First Compliant Deposit:	26 April 2022
Date of Acceptance:	4 April 2022
Last Modified:	11 Oct 2023 18:50
URI:	https://orca.cardiff.ac.uk/id/eprint/149232

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