Nasal antivirals block SARS-CoV-2 infection in mice

Colored scanning electron micrographs of cells infected with a mutant strain of SARS-CoV-2 virus particles (purple) (yellowish brown) isolated from a patient sample.Credit: NIAID Integrated Research Facility

SARS-CoV-2, the virus that causes COVID-19, has been continuously mutated since its emergence in late 2019. This rapid evolution poses challenges for vaccines and treatments designed to target viruses. Currently, booster shots are needed to produce antibodies to repel the Omicron variant of SARS-CoV-2. And some combinations of antibody treatments approved early in the pandemic do not work well against Omicron.

Another approach to treating COVID-19 is Human cells Used by viruses to infect them. These proteins change little over time.

A team led by Dr. Hector Aguilar-Carreño of Cornell University and a Canadian collaborator is developing a compound that can block one such protein called TMPRSS2.Viruses have spike proteins Cell membrane Go inside the cell.

This work was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) at NIH. The results were published on March 28, 2022. Nature..

In cell experiments, some new compounds inhibited TMPRSS2 activity, some by more than 80%. Four of the most promising compounds worked well at very low concentrations and did not adversely affect normal cell survival.

Next, researchers screened these top candidates for their ability to prevent SARS-CoV-2 from infecting cells. The most effective compound, called N-0385, has significantly reduced the amount of virus that can invade cells from lung and colon tissue. Similar results were seen with new variants of the virus, including Delta.

Next, the team tested nasal delivery of N-0385 in a mouse model of severe COVID-19.Antiviral drug Nasal spray Treatment should have some potential benefits. SARS-CoV-2 enters the body mainly through the nose. Nasal drops can be easily used by people at home. Also, delivering the drug directly to the nose or lungs may reduce exposure to the rest of the body and limit side effects.

The researchers first administered N-0385 once daily, from 1 day to 6 days after virus exposure. None of the 10 mice treated with the control dose saline survived, but 7 of the 10 mice treated with N-0385 survived. Most of the surviving mice had little or no lung damage.

when team Experiments were repeated on shorter courses of treatment from 1 day to 2 days after exposure, and all 10 mice fed N-0385 survived. In contrast, only one in ten who received saline was alive. Samples taken 3 days after infection were found to be 97% less virus in the lungs of mice treated with N-0385. When the experiment was performed with only a single dose of N-0385 given on the day of infection, the treated mice also showed high survival rates.

Treatment also showed protection against delta mutants. These experiments were done before Omicron.However, because N-0385 works on the host cellIt may be possible to block various variants from the use of target host proteins.

“N-0385 therapy is easier and less expensive to mass produce than other types of COVID-19 treatment, including: Monoclonal antibody“Aguilar-Carreño says.

Researchers are currently working with biotechnology companies to create drug versions for testing people.

Promising nasal drops may prevent and treat COVID-19

For more information:
Tirosh Shapira et al, a TMPRSS2 inhibitor, plays a prophylactic and therapeutic role in pan-SARS-CoV-2. Nature (2022). DOI: 10.1038 / s41586-022-04661-w

Quote: Nasal antivirals block SARS-CoV-2 infection in mice (April 16, 2022).

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Nasal antivirals block SARS-CoV-2 infection in mice

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