As the novel coronavirus continues to plague the world with its mutated variants, scientists have become more eager to find more solid solutions aside from the vaccines. One of the latest scientific endeavors of researchers drove them to come up with compounds capable of blocking a protein needed by SARS-CoV-2 to gain entry to cells. These compounds were put to a test in mice clinical trials, and they yielded positive outcomes.
Due to mutations, several of the available antibody treatments no longer work well against the newer variants of the coronavirus, especially against omicron. This pushed a team of researchers led by Dr. Hector Aguilar-Carreño from Cornell University and collaborators in Canada to turn their attention to an alternative approach that focused more on blocking the proteins in human cells needed by the virus to fuse with the cell membrane and enter the cells.
Human Cell Protein Regulation
For their study, published in the journal Nature, the team developed several compounds that inhibited the activity of the protein called TMPRSS2 in human cells. This protein is needed by SARS-CoV-2 because it helps the spike protein fuse with the cell membrane and facilitates the infection process. When the protein is regulated, the virus’ ability to enter the cell is impacted.
The compounds that the scientists came up with were able to inhibit the activity of TMPRSS2 in human cells by more than 80%. Four of them showed very promising results since they worked well even at very low concentrations, and they did not affect the survivability of the tested human cells.
Among the top candidates in the experiments, the compound called N-0385 proved to be the most effective since it substantially reduced the virus that could penetrate the cells derived from the lungs and colon tissues. It worked well against the newer variants of the coronavirus, including the more serious delta strain.
Nasal Spray Treatment
Aguilar-Carreño and his team tested N-0385’s efficiency when used as a nasal spray in mice experiments. They started by administering the spray once a day, starting a day before the viral exposure through 6 days afterward. Seven out of the ten mice survived the COVID-19 infection with little to no lung damage. On the other hand, all ten mice that received the control dose of saline did not survive.
The researchers also tried a shorter course approach by administering the spray one day before viral exposure through 2 days afterward. With this setup, all ten survived. Meanwhile, only one survived in the saline group. After analyzing the samples taken from the third day after infection, the team found that the mice treated with the compound had 97% less virus in their lungs. They then tried administering only a single dose of the compound given on the day of infection and found that the mice had a high survival rate.
Although the experiments showed promise, Medical Xpress pointed out that all of them were conducted before omicron came into the picture. But there is hope that N-0385 could also protect host cells from omicron and its newer subvariants because it targets a part of the human cell instead of the spike proteins on the virus. Aguilar-Carreño also pointed out that, if ever, their antiviral nasal spray would be less expensive to mass-produce than other types of COVID-19 treatments.
“There are very few, if any, small molecule antivirals that have been discovered that work prophylactically to prevent infection. This is the first of its kind. One advantage is that it works early in the infection, even after someone has already acquired the virus,” Aguilar-Carreño told Cornell Chronicle.