Antivirals used to treat coronavirus in cats also work against SARS-CoV-2

Researchers at the University of Alberta are preparing to start clinical trials of a drug used to cure a deadly disease caused by a coronavirus in cats that they expect will also be effective as a treatment for humans against COVID-19 .

“In just two months, our results have shown that the drug is effective in inhibiting viral replication in cells with SARS-CoV-2,” said Joanne Lemieux, a professor of biochemistry at the Faculty of Medicine & Dentistry.

“This drug will most likely work in humans, so we are encouraged that it will be an effective antiviral treatment for COVID-19 patients.”

The drug is a protease inhibitor that interferes with the virus’ ability to replicate, thus ending an infection. Proteases are key to many bodily functions and are common targets for medicines to treat everything from high blood pressure to cancer and HIV.

First investigated by U of A chemist John Vederas and biochemist Michael James after the outbreak of severe acute respiratory syndrome (SARS) in 2003, the protease inhibitor was further developed by veterinary researchers who showed that it cures a disease that is fatal in cats.

The work to test the coronavirus that causes COVID-19 was a collaboration between four U-A laboratories, led by Lemieux, Vederas, professor of biochemistry Howard Young, and the founding director of the Li Ka Shing Institute of Virology. Lorne Tyrrell. Some of the experiments were performed by the Stanford Synchrotron Radiation Lightsource Structural Molecular Biology program.

Their findings were published today in the peer-reviewed journal Nature communication after they were first posted on BioRxIV, a research website.

“There’s a rule with COVID research that all results must be made public immediately,” Lemieux said, so they were posted before being peer-reviewed.

She said interest in the work is high, with the paper being accessible thousands of times as soon as it was posted.

Lemieux explained that Vederas synthesized the compounds, and Tyrrell tested them against the SARS-CoV-2 virus in test tubes and in human cell lines. The Young and Lemieux groups then revealed the crystal structure of the medicine as it binds to the egg white.

“We determine the three-dimensional shape of the protease with the drug in the active side-pocket, which is the mechanism of inhibition,” she said. “This will allow us to develop even more effective medicines.”

Lemieux said she will continue testing inhibitor modifications to make it an even better fit in the virus.

But she said the current drug shows enough antiviral action against SARS-CoV-2 to proceed immediately after clinical trials.

“Typically for a drug to go into clinical trials, it needs to be confirmed in the lab and then tested in animal models,” Lemieux said. “Because this drug has already been used to treat cats with coronavirus, and it is effective with little to no toxicity, it has already passed through these stages and with this we can move forward.”

“Because of the strong data we and others have collected, we are conducting clinical trials for this drug as an antiviral for COVID-19.”

The researchers have partnered with Anivive Life Sciences, a veterinary medicine company that develops the medicine for cats, to create the quality and quantity of medicines needed for human clinical trials. Lemieux said it is likely to be tested in Alberta in combination with other potent antiviral drugs such as remdesivir, the first treatment approved for conditional use in some countries including the United States and Canada.