The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.
| Title: | The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses. |
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| Authors: | Saud Z; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Tyrrell VJ; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Zaragkoulias A; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Protty MB; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Statkute E; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Rubina A; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Bentley K; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; White DA; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Rodrigues PDS; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Murphy RC; Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA.; Köfeler H; Core Facility Mass Spectrometry, Medical University of Graz, Graz, Austria.; Griffiths WJ; Medical School, Swansea University, Swansea, United Kingdom.; Alvarez-Jarreta J; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Brown RW; ENT Department, Betsi Cadwaladr University Health Board, Wrexham Maelor Hospital, Wrexham, United Kingdom.; Newcombe RG; Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom.; Heyman J; Division of Surgery, Cardiff and Vale University Health Board, Cardiff, United Kingdom.; Pritchard M; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, United Kingdom.; Mcleod RW; Division of Surgery, Cardiff and Vale University Health Board, Cardiff, United Kingdom.; Arya A; ENT Department, Betsi Cadwaladr University Health Board, Wrexham Maelor Hospital, Wrexham, United Kingdom.; Lynch CA; Anaesthetics and Critical Care Directorate, Cwm Taf University Health Board, Royal Glamorgan Hospital, Llantrisant, United Kingdom.; Owens D; Division of Surgery, Cardiff and Vale University Health Board, Cardiff, United Kingdom.; Jenkins PV; Haemostasis Diagnosis and Research, University Hospital Wales, Cardiff, United Kingdom.; Buurma NJ; Physical Organic Chemistry Centre, School of Chemistry, Cardiff University, Cardiff, United Kingdom.; O'Donnell VB; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom. Electronic address: o-donnellvb@cardiff.ac.uk.; Thomas DW; Advanced Therapies Group, School of Dentistry, Cardiff University, Cardiff, United Kingdom. Electronic address: thomasdw2@cardiff.ac.uk.; Stanton RJ; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom. Electronic address: StantonRJ@cardiff.ac.uk. |
| Source: | Journal of lipid research [J Lipid Res] 2022 Jun; Vol. 63 (6), pp. 100208. Date of Electronic Publication: 2022 Apr 15. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2021- : [New York] : Elsevier; Original Publication: Memphis, Lipid Research, inc. |
| MeSH Terms: | Mouthwashes*/pharmacology ; COVID-19*; Antiviral Agents ; Cetylpyridinium ; Humans ; Lipids ; Povidone-Iodine ; RNA, Viral ; SARS-CoV-2 |
| 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.; (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Conflict of interest Venture Life Group plc and Johnson & Johnson provided information on mouthwash formulations employed in the in vitro study. Venture Life Group partfunded the clinical study but had no input in study design, data analysis, or drafting of the article. The authors declare that they have no conflicts of interest with the contents of this article. |
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| Grant Information: | MR/S00971X/1 United Kingdom MRC_ Medical Research Council |
| Contributed Indexing: | Keywords: CPC; aminophospholipids; cetylpyridinium chloride; clinical trials; coagulation; inflammation; lipidomics; mouthwash; phospholipids; virology |
| Substance Nomenclature: | 0 (Antiviral Agents); 0 (Lipids); 0 (Mouthwashes); 0 (RNA, Viral); 85H0HZU99M (Povidone-Iodine); CUB7JI0JV3 (Cetylpyridinium) |
| Entry Date(s): | Date Created: 20220418 Date Completed: 20220628 Latest Revision: 20250530 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9010312 |
| DOI: | 10.1016/j.jlr.2022.100208 |
| PMID: | 35436499 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't