Nasal sprays may be a promising first line of defense against SARS-CoV-2 infection.

Nasal sprays may be a promising first line of defense against SARS-CoV-2 infection.

What you need to know

Prevention is the best medicine, and COVID-19 vaccines block most SARS-CoV-2 infections. But vaccines are fighting a changing opponent. New methods of fast-acting COVID-19 prevention are being researched to make it safer to be in large public gatherings like sporting events or concerts.

Researchers supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) have developed a nasal spray that has the potential to not only treat COVID-19 but also prevent SARS-CoV-2 infection in a way that the virus can’t mutate to avoid. The experimental drug works in mice, and researchers believe it may be effective in humans.

What did the researchers do?

Researchers have looked for ways to prevent SARS-CoV-2 infection that the virus can’t learn to dodge or evade by mutating. To infect a cell, the virus tricks several of that cell’s proteins, including one called TMPRSS2, to gain entry. Researchers began to work on compounds that stifle TMPRSS2’s ability to interact with the viral protein.

The researchers picked four compounds that worked at very low concentrations and did not negatively affect the host cells. Those compounds were tested in human lung and colon cells that were then exposed to SARS-CoV-2. The most promising compound, N-0385, virtually stopped infection in its tracks. Because N-0385 was suitable for use as a nasal spray, researchers used a mouse model that develops severe COVID-19 and gave the mice either N-0385 or control doses of saline in their noses.

The researchers first tried one dose a day for seven days, starting a day before SARS-CoV-2 infection. When treated with N-0385, 70% of the mice survived and had little to no lung damage. When the treatment course was shortened to four days, starting one day before infection, all 10 of the mice treated with N-0385 survived. Only one of the 20 mice given saline survived.

Mice treated with just a single dose of N-0385 on the day they were infected had a high survival rate as well.

Why is this research important?

COVID-19 vaccines teach the immune system to recognize a particular protein on SARS-CoV-2 that is known as the spike protein. But the spike protein may mutate to evade immune response.

TMPRSS2 is a protein in mouse and human cells that SARS-CoV-2 uses as a gateway to infect humans. By blocking that access, compounds that target TMPRSS2 have the potential to be effective against both current and future variants.

Because we get infected with SARS-CoV-2 primarily by breathing it in, a nasal spray might be an easy and efficient way to offer protection against the virus, especially in crowded places. Researchers plan to continue testing the timing of when N-0385 should be administered and to expand testing into human clinical trials.

Where can I go to learn more?

Nasal antiviral blocks SARS-CoV-2 infection in mice

  • More information about the results of the study, which was funded in part by NIAID.

Finding Effective Treatments for SARS-CoV-2 Variants

  • The Coronavirus Immunotherapy Consortium identified new candidate drugs based on monoclonal antibodies in work funded by NIAID.

Understanding the Range of Reactions to SARS-CoV-2

  • In a study funded by NIAID, researchers are using mice to look for genes that account for different COVID-19 symptoms.



Lee, K. (2022, April 27). Cornell research team to develop COVID-19 nose spray treatment. Cornell Daily Sun.

Shapira, T., Monreal, I. A., Dion, S. P., Buchholz, D. W., Imbiakha, B., Olmstead, A. D., Jager, M., Désilets, A., Gao, G., Martins, M., Vandal, T., Thompson, C. A. H., Chin, A., Rees, W. D., Steiner, T., Nabi, I. R., Marsault, E., Sahler, J., Diel, D. G., . . . Jean, F. (2022). A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic. Nature, 10.1038/s41586-022-04661-w. Advance online publication.


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Page last updated: June 16, 2022