The compound prevents SARS-CoV-2 from entering mouse cells

Researchers have developed compounds that interfere with many of the key features of the virus that allow it to invade human cells.

Researchers have studied a compound called MM3122 in cells and mice. When given in the early stages of infection, researchers show it as a promising new way to prevent infection and reduce the severity of COVID-19.

“The compounds we are developing prevent the virus from invading cells.”

Interestingly, this compound targets an important human protein called transmembrane serine protease 2 (TMPRSS2). coronavirus A harness for invading and infecting human cells.

“Although a good vaccine is now available for SARS-CoV-2, we need an effective antiviral drug to help reduce the severity of this pandemic,” said Biochemistry and Molecular Biophysics at the University of Washington School of Medicine. Senior author James W. Janetka, a professor of biophysics, said. In St. Louis.

“The compounds we are developing prevent the virus from invading cells. We are investigating treatment windows that can administer molecules to mice and protect them from disease. Our ultimate goal is to evolve the molecule into an inhibitor that can be taken by mouth, which could be an effective part of our arsenal of COVID-19 inhibitors. “

This new drug compound strongly blocks another related protein called TMPRSS2 and tryptase found on the surface of the lungs and other cells. SARS-CoV-2, which causes COVID-19, and many other viruses, including coronavirus and influenza, depend on these proteins to infect cells and spread throughout the lungs. After the virus latches into cells of the airway epithelium, the human protein TMPRSS2 cleaves the virus’s peplomer, activates the peplomer, mediates the fusion of the virus to the cell membrane, and initiates the process of infection. MM3122 blocks the enzymatic activity of the human protein TMPRSS2. When the enzyme is blocked, it disrupts peplomer activation and suppresses membrane fusion.

“The SARS-CoV-2 virus hijacks our own lung cell machine and activates it. Spike protein, It allows it to bind and invade lung cells, “says Janetka.

“By blocking TMPRSS2, if it can be considered a preventative drug in theory, it prevents the virus from invading other cells in the body or lung cells. Currently, COVID -Test this compound in mice in combination with other treatments that target other important parts of the virus to develop effective broad-spectrum antiviral theories that help with 19 and other viral infections. doing.”

When studying cells growing in a laboratory infected with SARS-CoV-2, MM3122 is far superior to remdesivir, a treatment already approved by the Food and Drug Administration for patients with COVID-19. Protected cells from viral damage. Acute safety studies in mice showed that high doses of the compound given for 7 days did not cause any noticeable problems. Researchers have also shown that the compound is equally effective against the original severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).

“Most inhibitors of viral infection work by blocking the step of replication when the virus enters the cell,” said Sean Welan, co-author and professor and director of molecular microbiology. Stated.

“Dr. Janetka identified and improved the molecule that prevents the virus from invading cells first. Since the target of MM3122 is the host protein, this also leads to the emergence of inhibitors resistant viruses. It can pose a bigger barrier to it. “

“This compound isn’t just for COVID-19,” Janetka adds. “It has the potential to potentially block viral entry into other coronaviruses and influenza viruses. All of these viruses rely on the same human protein to enter lung cells. Therefore, human proteins Blocking prevents viruses that try to hijack those proteins from entering the cell. “

Janetka and his colleagues are currently working with researchers at the National Institutes of Health (NIH) to test the effectiveness of MM3122 in the treatment and prevention of COVID-19 in animal models of the disease. In animal studies, the drug is given as an injection, but Janetka says she is working on an improved compound that can be taken orally. He is also interested in developing intranasal pathways that deliver drugs more directly to the nasal passages and lungs.

The study will be displayed in Minutes of the National Academy of Sciences..

In collaboration with the University of Washington’s Technology Management Office (OTM), Janetka co-founded a biotechnology startup called ProteXase Therapeutics. -CoV, and MERS-CoV. Vishnu C, co-author with Janetka. Damalanka is listed as the inventor of two patent applications from the University of Washington for these compounds. Janetka and co-author Lidijah Klampfer own a stake in ProteXase Therapeutics and have licensed two patent applications.

The work was funded by the Siteman Cancer Center. Burns-Jewish Hospital Foundation; National Institutes of Health (NIH); Campaign to Promote Research on Eosinophilia (CURED) Foundation; Rapid Grant from Emergent Ventures at Mercatus 9 Center. BMBFRAPID Consortium; COVIM Consortium; Lower Saxony; and German Research Foundation. Work at Live SARS-CoV-2 was funded by the Burroughs Welcome Foundation investigator for the Infectious Disease Cause Award.

sauce: Washington University in St. Louis