“Inhibitors of the main protease of SARS-CoV-2, like masitinib, could be a new potential way to treat COVID patients, especially in early stages of the disease,” said Prof. Savas Tay, who led the research.

“COVID-19 will likely be with us for many years, and novel coronaviruses will continue to arise. Finding existing drugs that have antiviral properties can be an essential part of treating these diseases.”

Researchers started screening a library of 1,900 safe drugs against OC43, that causes common cold and can be studied under regular biosafety conditions. They used cell cultures to determine the drugs’ effect on infection.

They tested top 30 drugs in cell cultures against the SARS-CoV-2 virus at the Howard Taylor Ricketts Laboratory, a BSL-3 facility at Argonne National Laboratory. Measurements in the high-containment lab revealed around 20 drugs that inhibit SARS-CoV-2.

They tested against the 3CL protease, the enzyme within coronaviruses that allows them to replicate inside a cell.

Masitinib completely inhibited the 3CL viral enzyme inside the cell, a fact that was confirmed by X-ray crystallography by Prof. Andrzej Joachimiak’s group at Argonne. The drug specifically binds to the 3CL protease active site and inhibits further viral replication.

“That gave us a strong indication of how this drug works, and we became confident that it has a chance to work in humans,” Drayman said.

Masitinib is currently only approved to treat mast cell tumors in dogs, but it has undergone human clinical trials for several diseases, including melanoma, Alzheimer’s disease, multiple sclerosis, and asthma.

It has been shown to be safe in humans but does cause side effects, including gastrointestinal disorders and edema, and could potentially raise a patient’s risk for heart disease.

They then tested the drug in a mouse model. They found that it reduced the SARS-CoV-2 viral load by more than 99 percent and reduced inflammatory cytokine levels in mice.

They also began to test the drug in cell cultures against other viruses and found that it was also effective against picornaviruses, which include Hepatitis A, polio, and rhinoviruses that cause the common cold.

They tested in cell cultures against three SARS-CoV-2 variants, Alpha, Beta, and Gamma, and found that it worked equally well against them, since it binds to the protease and not to the surface of the virus.

Now, the they are working with the pharmaceutical company that developed the drug to tweak the drug to make it an even more effective antiviral. Meanwhile, masitinib itself could be taken to human clinical trials in the future to test it as a COVID-19 treatment.

“Masitinib has the potential to be an effective antiviral now, especially when someone is first infected and the antiviral properties of the drug will have the biggest effect,” Drayman said.

“This isn’t the first novel coronavirus outbreak, and it’s not going to be the last. In addition to vaccines, we need to have new treatments available to help those who have been infected.”

Source: Medindia