Antiviral used to treat cat coronavirus also works against SARS-CoV-
2
Fast-tracked research leads to Phaseclinical trials

Date:
August 27, 2020
Source:
University of Alberta Faculty of Medicine & Dentistry
Summary:
Researchers are preparing to launch 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.



FULL STORY ========================================================================== Researchers at the University of Alberta are preparing to launch 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
at inhibiting viral replication in cells with SARS-CoV-2," said Joanne
Lemieux, a professor of biochemistry in the Faculty of Medicine &
Dentistry.

"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."
The drug is 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.

First studied by U of A chemist John Vederas and biochemist 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 work to test the drug against the coronavirus that causes COVID-19 was
a co-operative effort between four U of A laboratories, run by Lemieux, Vederas, biochemistry professor Howard Young and the founding director
of the Li Ka Shing Institute of Virology, Lorne Tyrrell. Some of the experiments were carried out by the Stanford Synchrotron Radiation
Lightsource Structural Molecular Biology program.



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

"There's a rule with COVID research that all results need to be made
public immediately," Lemieux said, which is why they were posted before
being peer- reviewed.

She said interest in the work is high, with the paper being accessed
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 drug as it binds with the protein.

"We determined the three-dimensional shape of the protease with the
drug in the active site pocket, showing the mechanism of inhibition,"
she said. "This will allow us to develop even more effective drugs."
Lemieux said she will continue to test modifications of the inhibitor
to make it an even better fit inside the virus.



==========================================================================
But she said the current drug shows enough antiviral action against
SARS-CoV- 2 to proceed immediately 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," Lemieux said. "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." The researchers have established a 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. 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.

The U of A researchers' work was funded by the Canadian Institutes of
Health Research, the Natural Sciences and Engineering Research Council
of Canada, Alberta Innovates, Li Ka Shing Institute of Virology and the
GSK Chair in Virology.


========================================================================== Story Source: Materials provided by University_of_Alberta_Faculty_of_Medicine_&_Dentistry.

Original written by Gillian Rutherford. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Wayne Vuong, Muhammad Bashir Khan, Conrad Fischer, Elena Arutyunova,
Tess
Lamer, Justin Shields, Holly A. Saffran, Ryan T. McKay, Marco J. van
Belkum, Michael A. Joyce, Howard S. Young, D. Lorne Tyrrell, John C.

Vederas, M. Joanne Lemieux. Feline coronavirus drug inhibits the
main protease of SARS-CoV-2 and blocks virus replication. Nature
Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-18096-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200827155006.htm

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