Make-up of SARS-CoV-2 outer envelope revealed

The molecular make-up of the fatty outer envelope of SARS-CoV-2 has been detailed for the first time, offering a new target for antivirals, British scientists have announced.

The findings also suggest that mouthwashes may be effective in purging the virus from the mouth during dental procedures.

Scientists at Cardiff University have shown the viral lipid envelope has significant differences from healthy host cell membranes.

This, they write in the *Journal of Lipid Research*, could mean there is potential for it to be selectively targeted.

Study co-author Professor Valerie O’Donnell, a lipid biochemist from the University’s School of Medicine, said: “While vaccines and antivirals have targeted proteins or the replication cycle of SARS-CoV-2, there has been little research into the lipid envelope to date.

“Our study has mapped this essential viral component – indeed, there has been very little research into any viral lipid envelopes so far. Addressing this knowledge gap could enable selective therapeutic targeting that avoids damaging host membranes.

“We also suspect the membrane won’t be impacted by mutation of the virus, unlike spike proteins, so it would be a consistent target.”

The team used mass spectrometry to create a detailed map of the lipid envelope, finding it was composed of mainly phospholipids. Unlike host cell membranes there was very little cholesterol.

This, says the team, suggests there is potential to target the virus with therapeutics in the oral cavity without damaging the body’s own cells.

As part of the same study, the team carried out a clinical trial in 27 hospitalised COVID-19 patients to establish if test oral rinses containing surfactants could reduce infectivity in the mouth.

The participants, all of whom had PCR-confirmed COVID-19 were given one of four different types of oral rinse: two containing cetylpyridinium chloride (CPC), one containing povidone-iodine and another containing saline.

The most effective was the rinse that contained CPC and isopropyl myristate: a single 30-second rinse in seven patients eliminated the virus in the saliva by 99.99% at one minute, and by 99.8% at 60 minutes. In three of the seven patients no live virus was detected in the saliva at any time after the initial rinse.

The rinses containing compounds such as povidone-iodine or saline had little to no effect, while the rinse containing CPC and benzoate did not have a persistent effect.

Study co-author Professor Richard Stanton, from the University’s School of Medicine, said: “The findings of our clinical trial suggest the lipid envelope could be targeted by specific formulations of oral rinses.

“Our results suggest certain mouthwashes could play a role in limiting COVID-19 exposure in healthcare settings, for example, destroying the virus for sufficient time to enable a dental or oral examination. It could also be a useful component of infection prevention and control for other respiratory enveloped viruses, such as influenza.”

The authors say it is important to note that mouthwash cannot target any virus in the lower respiratory tract.

Professor David Thomas, co-author from the University’s School of Dentistry, added that larger clinical trials and population-based studies are now needed to determine if oral rinses have any impact on COVID-19 transmission.

The SARS-CoV2 envelope differs from host cells, exposes pro-coagulant lipids, and is inactivated in vivo by oral rinses. *Journal of Lipid Research* 15 April 2022

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