BREAKING! COVID-19 Drugs: Canadian Study Shows That Feline Coronavirus Drug GC376 Has Efficacy Against SARS-CoV-2 And Could Work For Humans
: Canadian researchers from the University of Alberta are preparing to launch clinical trials of a drug called GC376 ( A prodrug of the parent drug called GC373) used to cure a deadly disease caused by a coronavirus in cats and they expect will also be effective as a treatment for humans against COVID-19 after successful vitro studies.
The study findings or the vitro trials are published in the journal: Nature Communications. https://www.nature.com/articles/s41467-020-18096-2
Dr Joanne Lemieux, a professor of biochemistry in the Faculty of Medicine & Dentistry told Thailand Medical News, "In just two months, our results have shown that the drug is effective at inhibiting viral replication in cells with SARS-CoV-2."
She added, "This prodrug GC376 and its parent GC373 is very likely to work in humans, so we're encouraged that it will be an effective antiviral treatment for COVID-19 patients."
The pharmaceutical compound is basically a protease inhibitor that interferes with the virus's ability to replicate, thus ending an infection. Proteases are key to many body functions and are common targets for drugs to treat everything from high blood pressure to cancer and HIV.
Initially studied by University of Alberta chemist Dr John Vederas and biochemist Dr Michael James following the 2003 outbreak of severe acute respiratory syndrome (SARS), the protease inhibitor was further developed by veterinary researchers who showed it cures a disease that is fatal in cats.
The study to test the drug against the coronavirus that causes COVID-19 was a co-operative effort between four University of Alberta laboratories, run by Dr Lemieux, Dr Vederas, biochemistry professor Dr Howard Young and the founding director of the Li Ka Shing Institute of Virology, Dr Lorne Tyrrell.
Certain of the experiments were carried out by the Stanford Synchrotron Radiation Lightsource Structural Molecular Biology program.
Dr Lemieux explained that Dr Vederas synthesized the compounds, and Dr 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 drug as it binds with the protein.
She added, "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."
Dr Lemieux said she will continue to test modifications of the inhibitor to make it an even better fit inside the SARS-CoV-2 coronavirus.
However she said the current drug shows enough antiviral action against SARS-CoV-2 to proceed immediately to clinical trials.
Dr Lemieux said. "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 is effective with little to no toxicity, it has already passed those stages and this allows us to move forward."&
As most animals with feline infectious peritonitis don’t show symptoms, some cats can develop severe illness if the virus mutates to infect a specific type of immune cell. When that happens, the coronavirus spreads throughout the cat’s body, sparking a deadly inflammatory reaction that can cause paralysis or fluid to accumulate in the lungs.
In a way, the cat coronavirus is similar to SARS-CoV-2. Both severe COVID-19 in people and feline infectious peritonitis cases are driven by a dysfunctional inflammatory immune response, says Julie Levy, a veterinarian at the University of Florida in Gainesville.
The prodrug GC376 works by preventing a key enzyme called M protease, which is found in a number of different coronaviruses, from chopping up long strings of viral proteins. RNA viruses like SARS-CoV-2 often make such protein strings that protease enzymes snip into smaller pieces that then help the virus make more of itself in a cell. Hindering the protease’s ability to cut can halt viral replication.
Dr Lemieux further added, "Because of the strong data that we and others have gathered we are pursuing clinical trials for this drug as an antiviral for COVID-19."
The study team have established collaboration with Anivive Life Sciences, a veterinary medicine company that is developing the drug for cats, to produce the quality and quantity of drug needed for human clinical trials.
Dr Lemieux said it will likely be tested in Alberta in combination with other promising antivirals such as remdesivir, the first treatment approved for conditional use in some countries including the United States and Canada.
Another study by researchers from the University of Arizona in Tucson led by Dr Jun Wang, a chemist who studies antiviral drug development, had also found that GC376 can stop the SARS-CoV-2 protease from working in a test tube. Dr Wang, who reported those results June in the journal Cell Research
, says his team is now testing the compound in mice models. https://www.nature.com/articles/s41422-020-0356-z
There is also another other cat drug, GS-441524, that has been effective against the feline coronavirus and is similar to remdesivir. The compounds have a similar chemical structure, though remdesivir has an additional part that better helps it get into cells. Both remdesivir and GS-441524, drugs developed by the biopharmaceutical company Gilead Sciences, based in Foster City, Calif., mimic a building block of the genetic molecule RNA, which makes up the coronavirus’s genetic material. As the virus replicates, it incorporates the copycat building block into its RNA, which prevents viral enzymes from adding more building blocks, stopping replication.
Another study published in July 21 study in the journal Cell Reports
found that the drug can inhibit SARS-CoV-2 replication in lab-grown monkey and human cells. Remdesivir, however, was more potent in human lung cells, while GS-441524 was more potent in the monkey cells. https://www.cell.com/cell-reports/pdf/S2211-1247(20)30921-9.pdf
Researchers and experts both warn that no one should ever attempt to self-treat with any drugs meant for veterinary purposes till researchers ascertain under proper and supervised clinical trials that these drugs actually are safe and effective in humans.
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