Can one nasal spray a day prevent COVID?

During the ordeal of the COVID-19 pandemic, Anne Moscona did not feel safe going to a restaurant or catching a flight. And she wished she could feel safe to see her immunocompromised relatives without inadvertently transmitting the new coronavirus to them. All of this made her work personal: for the past decade, Moscona, a molecular virologist, has been searching for compounds that could stop viruses in their tracks, before pathogens infect even a single cell in a person’s body.

Now, Moscona of Columbia University in New York and her colleagues have discovered a compound that could thwart SARS-CoV-2. Even better, it’s simply sprayed into the nose—no needle needed¹.

The spritz developed by Moscona’s team is one of a number of proposed nasal sprays to prevent SARS-CoV-2 infection. The sprays would be fast-acting and would be applied frequently, perhaps once or twice a day, to the place where the virus first took hold – the lining of the nose and throat. Unlike vaccines, which train the recipient’s immune system to build long-term protection, sprays are short-term compounds that would directly block the virus’s ability to enter cells. Several research teams have shown that such sprays are effective in protecting against SARS-CoV-2 infection in animals.

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If effective in humans, the compounds would be a welcome addition to the limited arsenal researchers have developed against the virus, says Donna Farber, an immunologist at Columbia University in New York. Vaccines protect against severe disease, COVID-19, but are less adept at preventing infection, and current antiviral drugs treat infection, not prevent it. The sprays could offer people another way to avoid infection in addition to — or instead of — wearing a face mask, especially in high-risk settings such as hospitals and restaurants. “They are definitely worth seeking out,” she says.

Despite the promise, these sprays have a long way to go: Funding and interest from pharmaceutical companies in human trials is limited, in part because trials to determine the effectiveness of prophylactics are large and expensive, Moscona says. And the sprays have to do the tough job of coating any surface the virus might attach to, because once a virus particle gets into even a few cells, a full-scale infection can progress quickly.

Virus block

Efforts to develop prophylactic treatments against the virus long predated COVID-19, says Wendy Barclay, a virologist at Imperial College London. Such research has paid off with a number of oral drugs, including oseltamivir (Tamiflu), which protects against influenza infection, and tenofovir-emtricitabine, which prevents HIV infection. But, Barclay says, there are no prophylactic nasal sprays other than First Defence, which is designed to act as a physical barrier against cold virus particles.

Prophylactic sprays have a simpler task than conventional antiviral drugs, such as Paxlovid, which are used in the first days of infection: preventing a single virus particle from infecting a cell is “a much easier task than suppressing the effects of millions of virus particles” in the days after infection, Barclay says.

Researchers have tested many types of compounds in nasal sprays to prevent SARS-CoV-2 infection. Among them are small antibody-like molecules called nanobodies, which disarm the virus by nesting in the nooks and crannies of viral proteins; short chains of amino acids called peptides; and small molecules that mimic proteins.

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The prophylactic developed by Moscona and her colleagues, for example, is a peptide that suppresses the virus’s mechanisms for binding to the host cell. This prevents the virus from delivering its genetic cargo into the cell, thereby blocking infection.

To test their peptide, Moscona and her colleagues injected it into the noses of ferrets once a day for two days and kept the treated animals together with another ferret infected with SARS-CoV-2. None of the six ferrets that received the peptide became infected with the virus, while all six ferrets that received the placebo dose did.¹. Before testing the peptide on humans, Moscona wants to replicate these results in another animal model, such as mice.

Another nasal spray compound, developed by Richard Leduc, a molecular pharmacologist at the University of Sherbrooke in Canada, and his colleagues, is a small molecule that inhibits a host enzyme that viral particles need to attach to a target cell. Leduc and his colleagues found that mice given nasal doses of the compound became infected with the coronavirus, but had much less virus in their lungs than mice given only saline.². Leduc and his colleagues are working to increase the effectiveness of the peptide by making it more stable and selective before moving on to human testing. Both Leduc and Moscona work with companies to market their products.

The challenge of a runny nose

Even if researchers find an antiviral compound that can be delivered as a nasal spray and that prevents coronavirus infections in humans, they still face the challenge of ensuring that the compound stays in the nasal lining long enough to be consistently effective. “Your nose and throat are inherently designed to get rid of things,” says Barclay. “You try to put something in there and your nose runs and flushes.”

Researchers could counter this by designing sprays that are applied more often, but Barclay warns that the more often people have to take the drug, the less likely they are to stick to the regimen. And although most SARS-CoV-2 infections begin in the nose, it may be necessary to coat the mouth and throat and even the lungs with the prophylactic agent, which would require delivery through a nebulizer.

Still, such a spray would be an important advance, especially in places where few people wear face masks, Barclay says. “If we had something that was invisible and that you controlled yourself and gave you the confidence to keep going, I think that would be a real game changer,” she says. “We could keep the kids in school.”