Cat antiviral that inhibits SARS-CoV-2 fast-tracked for human clinical trials

By Angela Betsaida B. Laguipo, BSNAug 31 2020

The coronavirus disease (COVID-19) pandemic has affected most countries worldwide, and with eight months passed since the virus first emerged, there are still no approved drugs or vaccines against it. Many clinicians have used antivirals intended for other infections in the hope that they will work against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.

Now, a team of researchers at the University of Alberta in Canada has identified viral inhibitors that they claim are potential candidates as a treatment for COVID-19. The team is set to launch clinical trials of the drug that is used as a treatment for a type of coronavirus in cats.

The drug

The drug, which is a dipeptide-based protease inhibitor, GC376, and its analog, GC373, interferes with the ability of the virus to replicate and infect. Proteases are critical to many body functions and are common targets for many drugs, including those against hypertension, human immunodeficiency virus (HIV), and cancer, among others.

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

"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," she added.

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. (Photo: Supplied)

The drug was first studied by the University of Alberta chemist John Vederas and biochemist Michael James after the 2003 outbreak of severe acute respiratory syndrome (SARS). The veterinary researchers developed the protease inhibitor and found that it cures a disease that is potentially fatal in cats.

The urgent need for a drug

The coronavirus pandemic is steadily growing, now affecting 188 countries and territories. As of writing, the number of cases has topped 25.12 million, while the number of deaths has reached more than 845,000. The United States remains the nation with the highest number of infections, reaching nearly 6 million cases, followed by Brazil, with more than 3.86 million confirmed cases.

With the pandemic spreading, scientists from all over the world are racing to find an effective vaccine and drug against the virus. Many turned to drug repurposing, wherein they use antivirals against other infections in the hopes that these will be effective.

Fatalities have been continuously added to the coronavirus toll, with some populations at higher risk of death. These include the elderly, those with underlying health conditions, and those who are immunocompromised. Some medical conditions that may aggravate COVID-19 complications include heart disease, high blood pressure, diabetes, obesity, kidney disease, and lung ailments.

Effective against SARS-CoV-2

This latest study, published in the journal Nature Communications, highlights the result of testing the protease inhibitors used in cats in SARS-CoV-2 cell culture.

The researchers noted that Vederas synthesized the compounds, and Tyrrel tested them against the SARS-CoV-2 virus in test tubes and human cell lines.

The team has found that GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture, making them strong candidates in treating human coronavirus infections because they have been successful in animals.

The crystal structure of the drug has been identified and described as it binds with the protein. The team also revealed the three-dimensional shape of the protease with the drug in the active site pocket, showing how it inhibits virus replication. With the new information and data, the team believes that the study will allow for the development of more effective drugs.

The researchers plan to test modifications of the inhibitor to develop it further so it can fit inside the virus. However, they emphasized that with the results of the study, showing that the drug is effective against SARS-CoV-2, it can already be used in human 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," Lemieux explained.

"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," she added.

The team partnered with Anivive Life Sciences, a veterinary company that develops drugs for cats to produce the needed drug for human clinical trials. They plan to test the drug in Alberta, combining it with other promising antivirals used against COVID-19, including remdesivir, which has been approved for conditional use in some countries, such as the United States and Canada.