Researchers at the Washington University School of Medicine in St. Louis have developed a new chemical compound that blocks SARS-CoV-2 from entering cells, as well as boasting strong potential to be used against other coronaviruses. Most recently the compound has been studied in cells and mice, with initial results being promising.
How does it work?
- The compound, which has been named MM3122, works by targeting a key human protein called transmembrane serine protease 2 (TMPRSS2), the protein that coronaviruses harness to enter and infect human cells. It blocks this protein and another related protein called matriptase, found on the surface of the lung and other cells.
- Usually, the protein TMPRSS2 allows the spike protein of the virus to be released, initiating infection via fusion of the viral and cellular membranes. However the new compound MM3122 prevents that from happening, by blocking the enzymatic activity of the protein TMPRSS2. In simpler terms, the new compound will stop infection from taking place, by blocking the enzymatic activity of the protein which allows the virus to enter host cells.
One current treatment that is used for SARS-CoV-2 is remdesivir, however in comparison lab studies on infected cells showed that the new MM3122 compound gave much higher levels of protection from viral damage. Furthermore the researchers found that in addition to being an effective treatment for SARS-CoV-2, the compound was also effective against SARS and MERS, two other types of coronaviruses. This means that the compound could be used as an effective treatment for all three coronaviruses, rather than targeting only one. Initial safety tests on mice during seven days also showed promising results, with no noticeable problems seen even after large doses.
“The majority of inhibitors of viral infection work by blocking steps of replication once the virus is inside the cell,” said co-author Sean Whelan, PhD, the Marvin A. Brennecke Distinguished Professor and head of the Department of Molecular Microbiology. “Dr. Janetka has identified and refined a molecule that stops the virus from entering the cell in the first place. As the target of MM3122 is a host protein, this may also pose a larger barrier to the emergence of viruses that are resistant to the inhibitor.”
Currently the drug has been given injection during animal studies, but researchers are working on ways to develop an improved compound which could be taken orally, or intranasal routes that would be able to deliver the drug more directly into the nasal and lung passages.