In mice, researchers discovered that a novel drug administered as a nasal spray is very successful at preventing and treating COVID-19 caused by the Delta variation.
The researchers believe this is the first medication of its kind to be demonstrated effective against all COVID-19 variants of concern reported to far, including alpha, beta, gamma, and delta, according to UBC, Université de Sherbrooke, and Cornell University. The study, which was published in Nature today, paves the way for the development of a human medicinal spray.
Concerning variants, such as the recent Omicron variants, have reduced vaccine effectiveness, but senior author Dr. François Jean, an associate professor in the UBC department of microbiology and immunology, says preliminary results from his team show promise that N-0385 can also block Omicron variant infections in human lung cells.
“Our unpublished results represent encouraging findings with the current rapid propagation of Omicron BA.2 around the world.”
“Unfortunately, with another wave of an Omicron variant hitting the U.K., 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 defense against COVID-19 variants of concern,” says Dr. Jean, founder of FINDER, the state-of-the-art level three biocontainment facility where the work on SARS-CoV-2 variants was conducted.
N-0385 is a specially developed chemical that inhibits the action of a specific human enzyme utilized by the virus to infect a host cell. Drs. Richard Leduc, Éric Marsault, Pierre-Luc Boudreault, and their colleagues at Université de Sherbrooke developed the tiny chemical.
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.
Dr. François Jean
Researchers from UBC evaluated four versions, including Delta, in human lung cells and organoids, which are tissue cultures that may imitate the organ they’re derived from, and discovered that N-0385 prevents infection while causing no harm.
“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,” says co-author Dr. Andrea Olmstead (she/her), research associate in the department of microbiology and immunology.
In a preprint, Cornell University researchers led by Associate Professor Hector Aguilar-Carreno demonstrated that genetically engineered mice infected with the virus that causes COVID-19 were given a daily dose of the compound in a nasal spray for four days after being infected with the virus that causes COVID-19. Only 20% of the untreated mice survived infection, but all ten of the treated mice did.
In a new study, N-0385 was tested against the Delta version of COVID-19, and it was discovered that it not only helped with COVID-19 prevention, but also treatment 12 hours after infection, including infection-related weight loss and viral levels in the mice’s lungs, as compared to controls.
Because the enzyme that N-0385 targets is found in nasal cells, where the virus is most likely to penetrate, a nasal spray is the most convenient and effective approach to administer the drug.
Furthermore, unlike other enzymes and COVID-19 variants, no mutations related to the virus that causes COVID-19 have been detected in the mechanism of this enzyme, making it a suitable target for protection against future strains of the virus, according to Dr. Jean.
According to Dr. Jean, the chemical has the potential to be employed as a broad-spectrum treatment against other viruses that use the same mechanism, such as influenza A, H1N1, and C.
“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, because the spray is an entry inhibitor, it should be used in conjunction with other medications already on the market, he argues, because it prevents the virus from entering cells while other drugs suppress 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.”
To gain funds for clinical studies, the project teams are collaborating with Ebvia, a private corporation. Optimizing N-0385 when used in combination with recently approved medications to treat COVID-19 is one of the future research directions at UBC and Université de Sherbrooke.
The Coronavirus Variations Rapid Response Network, CIHR’s SARS-COV-2 variants supplement, Stream 2, CIHR COVID-Rapid Research Funding, and Genome BC Rapid Response Funding (RRF) for COVID-19 Research and Innovation Projects all contributed to this research.
