Could a nasal spray revolutionise treatment for the delta variant?

Could a nasal spray revolutionise treatment for the delta variant?
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A new compound delivered in a nasal spray is highly effective in preventing and treating the Delta variant of Covid in mice.

The study was a collaboration between the University of British Columbia (UBC), Université de Sherbrooke, and Cornell University and they believe the nasal spray is the first treatment of its kind to be effective against all COVID-19 variants reported to date.

The research was published in Nature.

Covid nasal spray development

The specifically designed compound, named N-0385, blocks a particular human enzyme’s activity used by the virus to infect a host cell. The small molecule was developed by Drs Richard Leduc, Éric Marsault, Pierre-Luc Boudreault and their team at Université de Sherbrooke. UBC researchers tested four variants, including Delta, in human lung cells and organoids, tissue cultures that can mimic the organ they are taken from and found that N-0385 inhibits infection, with no evidence of toxicity.

“The compound is unique because it blocks entry at the cell surface without having to get into the cell, which prevents it from causing any detectable cell damage. As well, it’s highly potent, in that it needs only a tiny amount to work very effectively,” said co-author Dr Andrea Olmstead, research associate in the department of microbiology and immunology.

In a preprint, the researchers at Cornell University led by Associate Professor Hector Aguilar-Carreno showed that genetically engineered mice infected with the COVID-19 virus and given a daily dose of the compound in the nasal spray for four days. All ten of the treated mice survived the infection, compared with only 20% of the untreated mice.

“Unfortunately, with another wave of an Omicron variant hitting the UK, Europe, and China and our knowledge of how these waves occur, this may be what we see in Canada in the near future. Once approved, this compound could be used in combination with already available drugs that inhibit the virus’ replication to provide a stronger defence against COVID-19 variants of concern,” said Dr Jean, founder of FINDER, the state-of-the-art level three biocontainment facility where the work on SARS-CoV-2 variants was conducted.

Preventing and treating COVID-19

The researchers noted in their study that N-0385 within the nasal spray was tested against the Delta variant and was found to help with preventing COVID-19 and treatment 12 hours after infection, including with infection-related weight loss, and levels of the virus in the mice lungs, compared with controls.

“The enzyme which N-0385 targets is present in nasal cells, where the virus tends to enter, making a nasal spray the most practical and effective way to administer the compound. In addition, no mutations relating to the virus which causes COVID-19 have been found in this enzyme’s mechanism so far, as has occurred with other enzymes and COVID-19 variants, making it a useful target for defence against future strains of the virus,” stated Dr Jean.

“The compound has the potential to be used as a broad-spectrum treatment against other viruses which use the same mechanism. Even not knowing what you’ve been infected with during flu season, you could potentially be prescribed a nasal spray to treat coronaviruses and the flu.”

However, the nasal spray should be used in combination with other drugs already on the market, he further commented, as the compound is an entry inhibitor, blocking entry of the virus to cells while other drugs reduce replication.

“The big picture is, there are multiple steps in the life cycle of a virus. The first step is entering a cell to pass on genetic material, then it goes on to replicate. So, you would use both drugs: N-0385 could block most of the virus’ entry, making less work for the replicator drug.”



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