Scientists from the United States have created a chemical compound that prevents a number of viruses from entering human cells.
The compound, dubbed MM3122, is a promising way to prevent infection or reduce the severity of COVID-19 when applied early in the course of infection, the researchers said.
Interestingly, this compound does not act on virus particles, but on a human protein: transmembrane serine protease 2 (TMPRSS2). Coronaviruses use it to enter human cells to subsequently take over their “production conveyors”, to make many copies of the pathogen, which then continue to invade the body.
“Excellent vaccines are now available for SARS-CoV-2, but we still need effective antiviral drugs to help tackle this pandemic,” says lead author James W. Janetka of the University of Washington, St. Louis. – The compound we are developing prevents the virus from entering cells.
We are investigating a therapeutic window within which a molecule can be administered to mice to protect them from disease. Our ultimate goal is to turn molecules into an inhibitor that can be ingested and that can be an effective weapon in our arsenal of COVID-19 inhibitors. “
The new drug compound effectively blocks TMPRSS2 and another related protein, matriptase, which are found in lung tissue.
Many viruses, including SARS-CoV-2 and the influenza virus, infect cells and spread through the tissues of the lungs thanks to these proteins. After the virus enters the surface of the airway epithelial cell, the human TMPRSS2 protein interacts with the virus spike protein, thereby activating it. This initiates the infection process.
MM3122 blocks the enzymatic activity of the human TMPRSS2 protein. When the enzyme is blocked, it interrupts the activation of the spine protein and inhibits the fusion of the viral envelope with the cell membrane.
“By blocking TMPRSS2, the drug prevents the penetration of the virus […] into lung cells, if theoretically used as a prophylactic agent.
We are currently testing this compound in mice in combination with other drugs that target other key parts of the virus to develop an effective broad-spectrum antiviral therapy that will benefit COVID-19 and other viral infections, ”added Professor Janetka.
We add that while the authors of the work studied the effect of MM3122 on cells grown in the laboratory, infected with SARS-CoV-2. The drug protected cells from infection much better than remdesivir, approved for the treatment of COVID-19 by the US Food and Drug Administration.
A safety test in mice showed that large doses of the new compound given over seven days did not cause any discernible health problems in the animals.
The researchers also demonstrated that the compound is just as effective against the original SARS-CoV coronavirus, which causes severe acute respiratory syndrome, and the MERS-CoV coronavirus, which causes Middle East respiratory syndrome.
In animal studies, the drug was administered by injection, but Zhanetka and colleagues are working to ensure that the new drug can be taken orally in capsules or tablets.
Scientists are also interested in developing an intranasal drug that delivers drugs directly to the nasal passages and lungs.
A description of the new drug trials was published in the scientific journal PNAS.
As a reminder, we previously wrote that a licensed cholesterol-lowering drug is also effective against covid. In addition, we talked about how anti-COVID-19 nanobodies stop the virus already in the respiratory tract. We also reported on the development of an intranasal vaccine against the new coronavirus.
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