Researchers to launch clinical trials to test potential COVID-19 drug

A group of scientists from the University of Alberta is preparing to initiate clinical trials of a drug used for treating a lethal disease caused by the novel coronavirus in cats.

Researchers to launch clinical trials to test potential COVID-19 drug
Biochemist Joanne Lemieux worked with three other U of A researchers on a new study showing that a drug that cures deadly peritonitis in cats also works well enough against the coronavirus that causes COVID-19 to fast-track it into human clinical trials. Image Credit: University of Alberta.

According to the researchers, this drug may also be effective for treating humans against the COVID-19 infection.

In just two months, our results have shown that the drug is effective at inhibiting viral replication in cells with SARS-CoV-2. This drug is very likely to work in humans, so we’re encouraged that it will be an effective antiviral treatment for COVID-19 patients.”

Joanne Lemieux, Professor of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta

The target drug is a protease inhibitor that disrupts the ability of the virus to replicate, thereby leading to an infection. Proteases are crucial to several functions in the body and are standard drug targets for treating everything from HIV to high blood pressure and cancer.

The protease inhibitor was initially investigated by the University of Alberta chemist John Vederas and also by a biochemist Michael James after the 2003 outbreak of the severe acute respiratory syndrome (SARS) virus. This inhibitor was additionally developed by veterinary scientists, who demonstrated that it also treats a disease that is lethal in cats.

The study to test this drug against the coronavirus responsible for causing the COVID-19 infection was a collaborative effort between four University of Alberta laboratories, managed by Lemieux; Vederas; Howard Young, a biochemistry professor; and Lorne Tyrrell, the founding director of the Li Ka Shing Institute of Virology. The Stanford Synchrotron Radiation Lightsource Structural Molecular Biology program also helped perform some of the experiments.

The study results were recently published in Nature Communications—a peer-reviewed journal—after they were initially reported on a research website, BioRxIV.

There’s a rule with COVID research that all results need to be made public immediately,” added Lemieux, which is why they were published before they were peer-reviewed.

Lemieux added that the study has attracted huge interest, with the article being accessed by an unlimited number of times once it was reported.

Lemieux elaborated that Vederas produced the compounds, and Tyrrell verified them against the SARS-CoV-2 virus in human cell lines as well as in test tubes. Later, the teams of Young and Lemieux showed the crystal structure of the drug as it attaches to the protein.

We determined the three-dimensional shape of the protease with the drug in the active site pocket, showing the mechanism of inhibition. This will allow us to develop even more effective drugs.”

Joanne Lemieux, Professor of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta

Lemieux added that she would continue to verify the inhibitor changes, with the aim of making it an even better fit within the virus.

However, she also added that the present drug has adequate antiviral action against the SARS-CoV-2 virus to proceed directly to clinical trials.

Typically for a drug to go into clinical trials, it has to be confirmed in the lab and then tested in animal models. Because this drug has already been used to treat cats with coronavirus, and it's effective with little to no toxicity, it's already passed those stages and this allows us to move forward. Because of the strong data that we and others have gathered we’re pursuing clinical trials for this drug as an antiviral for COVID-19.”

Joanne Lemieux, Professor of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta

The team has developed an association with Anivive Life Sciences, a veterinary medicine firm that is creating the drug for cats, to generate the quantity and quality of drug required for human clinical trials.

Lemieux concluded that the drug would perhaps be examined in Alberta along with other potential antivirals like remdesivir, the initial treatment approved for conditional use in certain nations, such as Canada and the United States.

Source:
Journal reference:

Vuong, W., et al. (2020) Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nature Communications. doi.org/10.1038/s41467-020-18096-2.

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