Scientists at the University of Alberta have shown that the drug
remdesivir is highly effective in stopping the replication mechanism of
the coronavirus that causes COVID-19, according to new research
published today in the
Journal of Biological Chemistry.
The paper follows closely on research published by the same lab in
late February that demonstrated how the drug worked against the Middle East Respiratory Syndrome (MERS) virus, a related coronavirus.
“We were optimistic that we would see the same results against the
SARS-CoV-2 virus,” said Matthias Götte, chair of medical microbiology
and immunology at U of A.
“We obtained almost identical results as we reported previously with MERS, so we see that remdesivir is a very
potent inhibitor for coronavirus polymerases.”
Götte’s new paper demonstrates how remdesivir, developed in 2014 to
fight the Ebola epidemic, works in detail. He likens the polymerase to
the engine of the virus, responsible for synthesizing the virus’ genome.
“If you target the polymerase, the virus cannot spread, so it’s a very logical target for treatment,” Götte said.
The lab’s work shows how remdesivir tricks the virus by mimicking its building blocks.
“These coronavirus polymerases are sloppy and they get fooled, so the
inhibitor gets incorporated many times and the virus can no longer
replicate,” Götte explained.
He said the evidence from his group, along with previously published
studies in animal and cell culture models, means that remdesivir can be
classified as a “direct-acting antiviral” against SARS-CoV-2, a term
first used to describe newer classes of antivirals that interfere with
specific steps of the hepatitis C virus (HCV) life cycle.
He said the discovery of that direct action reinforces the promise of
clinical trials for remdesivir in COVID-19 patients, which are already
underway around the world.
While Götte said the evidence justifies clinical trials, he cautioned
that the results obtained in the lab cannot be used to predict how the
drug will work with people.
“We’ve got to be patient and wait for the results of the randomized
clinical trials,” said Götte, whose research was funded by the Canadian
Institutes of Health Research, Alberta’s Major Innovation Fund and
Gilead Sciences, which manufactures remdesivir.
The Götte lab previously worked on human immunodeficiency
virus
(HIV) and HCV, but a couple of years ago switched to focus on viruses
with the highest epidemic potential. The World Health Organization (WHO)
issued its list of the top pathogens likely to cause severe outbreaks,
including Ebola, Lassa and coronaviruses, in 2015.
“In that sense we were prepared because my lab specializes in viral
polymerases,” said Götte, adding that his next step will be to use his
lab’s tools to evaluate other promising antivirals.
He is optimistic that the unprecedented amount of research going on
worldwide and the high level of co-operation between researchers will
lead to the discovery of one or more effective treatments for COVID-19.
“We are desperate, but we still have to keep the bar high for anything that we put into clinical trials,” he said.
Remdesivir is one of several drugs being fast-tracked into trials by
the World Health Organization, comparing potential treatments in
hospitalized COVID-19 patients in a dozen countries, including Canada.
Götte said we can expect results from important
clinical trials as early as April or May.
Götte said it is disappointing that antivirals discovered at the time
of the severe acute respiratory syndrome (SARS) outbreak of 2003—which
might have been effective against COVID-19 too—were never translated
into widely available treatments, largely because of the huge cost
involved in developing new drugs.
“This time around it’s obvious that we have to cross the finish line,” he said.
“Ten billion dollars, it seems a lot, a huge amount,” Götte said.
“But in the context of this pandemic and the costs associated with this
pandemic, it’s nothing.”
