The SARS-CoV2 envelope is distinct from host membranes, exposes pro-coagulant lipids, and can be inactivated in vivo by surfactant-containing oral rinses

Abstract

The lipid envelope of SARS-CoV2 is an essential component of the virus, however its molecular composition is unknown. Addressing this knowledge gap could support the design of anti-viral agents, and further understanding of viral interaction with extracellular host proteins, infectivity, pathogenicity, and innate immune system clearance. Lipidomics analysis of SARS-CoV2 particles generated from Vero or A549 cells revealed that the virus envelope comprised mainly of phospholipids (PL), primarily phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), with very little cholesterol, sphingolipids or other lipids, indicating significant differences from host membranes. Unlike healthy cellular membranes, procoagulant aminoPL (aPL), specifically PE and phosphatidylserine (PS), were present on the external side at levels far exceeding those seen on activated platelets. As a result, purified virions directly promoted coagulation. To investigate whether these differences enabled the viral envelope to be selectively targeted at relevant sites in vivo, we tested whether non-toxic oral rinses containing lipid disrupting chemicals could reduce viral infectivity. Products containing PL-disrupting surfactant solutions (cetylpyridinium chloride (CPC) or ethyl lauroyl arginate) met EN14476 virucidal standards in vitro, however products containing essential oils, PVP-I, or Chlorhexidine did not, nor did rinses containing components that altered the critical micelle concentration of CPC. This result was recapitulated in vivo, where a 30-second oral rinse with CPC-mouthwash eliminated live virus in the oral cavity of COVID19 patients for at least 1hr, while PVP-Iodine and saline mouthwashes were ineffective. Thus, the SARS-CoV2 lipid envelope is distinct from the host plasma membrane which may enable design of selective anti-viral approaches, it exposes PE and PS which may influence thrombosis, pathogenicity, and inflammation, and can be selectively targeted in vivo by specific oral rinses.

Disinfection and decontamination in the context of SARS‐CoV‐2‐specific data

“…152 In commercial products, it is not uncommon to see ethanol or propanol combined with other potentially effective agents such as surfactants or quaternary ammonium compounds. 81,82,142,161,167,169 It is proposed that a concomitant surfactant may enhance efficacy. 161…”

“…Chlorhexidine products do variably achieve anti‐SARS‐V‐2 activity with concentrations ranging from 0.05% to 1%. 49 , 152 , 158 , 169 They appear to be less effective than alcohols and have differential action depending on the milieu. 158 Some residual antiviral activity may be possible.…”

“…As an extension of applying topical disinfectants, several studies have assessed various topical mucosal anti‐SARS‐CoV‐2 agents. 150 , 165 , 169 , 172 , 173 Conceivably, such use could be of potential value for the prevention of both infection acquisition or secondary spread. For example, the focused use of these agents in dental offices to mitigate potential transmission has been considered to be useful.…”

“…Formulations including hydrogen peroxide, benzalkonium chloride, dequalinium chloride, chlorhexidine, cetylpyridinium chloride, octenidine dihydrochloride, povidone–iodine, alkaline solutions, ethanol, hexetidine, cyclodextrin, polyaminopropyl biguanide, bioflavonoids, hypochlorous acid, delmopinol, silver nanoparticles, combination surfactants, essential oils, hydroxyapatite, glycyrrhizic acid, and/or sodium fluoride have been assessed. 150 , 154 , 169 , 172 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 Efficacy during in vitro or in vivo experiments has yielded variable results. Komine et al 175 did not find efficacy for chlorhexidine.…”

“… 150 , 177 , 179 , 180 Cetylpyridinium chloride in various dilutions inactivates virus, and the mechanism of action in part appears to be related to the interruption of the Spike protein/receptor complex. 150 , 169 , 186 The degree of product dilution has a considerable impact. 150 , 176 Methods of virucidal determination have also been variable and have included genetic amplification (reverse transcription‐polymerase chain reaction [RT‐PCR]), antigen detection, and viral culture.…”