Study Finds Remdesivir Effective Against Key Coronavirus Enzyme That Causes COVID-19

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PICTURE
PICTURE: Matthias Götte (left) and Egor Tchesnikov are part of a team from the University of Alberta who discovered that remdesivir, a drug created to treat Ebola, is effective in stopping the coronavirus …
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Credit: Melissa Fabrizio

Scientists at the University of Alberta have shown that remdesivir is very 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 document closely follows research published by the same laboratory in late February that showed how the drug works against the Middle East respiratory syndrome virus (MERS), a related coronavirus.
“We were optimistic that we would see the same results against the SARS-CoV-2 virus,” said Matthias Götte, president of medical microbiology and immunology at the University of Alberta.
“We have obtained results almost identical to those previously reported with MERS, so we find that remdesivir is a very potent inhibitor of coronavirus polymerases. “
Götte’s new document shows how remdesivir, developed in 2014 to fight the Ebola epidemic, works in detail. He compares the polymerase to the engine of the virus, responsible for the synthesis of the genome of the virus.
“If you target the polymerase, the virus cannot spread, so it is a very logical target for treatment,” said Götte.
Laboratory work shows how remdesivir tricks the virus by mimicking its building blocks.
“These coronavirus polymerases are sloppy and they are wrong, so the inhibitor is incorporated several times and the virus can no longer replicate,” said Götte.
He said his group’s evidence, as well as 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 used to describe new classes of antivirals that interfere with specific stages in the life cycle of the hepatitis C virus (HCV).
He said the discovery of this direct action reinforces the promise of clinical trials for remdesivir in COVID-19 patients, which are already underway around the world.
Although Götte said the evidence supports clinical trials, he cautioned that laboratory results cannot be used to predict how the drug will work with people.
“We have to be patient and wait for the results of randomized clinical trials,” said Götte, whose research was funded by the Canadian Institutes of Health Research, the Alberta Major Innovation Fund and Gilead Sciences, which manufactures remdesivir.
Götte’s laboratory previously worked on the human immunodeficiency virus (HIV) and HCV, but a few years ago it turned to viruses with the greatest epidemic potential. The World Health Organization (WHO) released its list of the main pathogens that can cause serious epidemics, including Ebola, Lassa and coronaviruses, in 2015.
“In this sense, we were prepared because my laboratory specializes in viral polymerases,” said Götte, adding that his next step will be to use his laboratory tools to evaluate other promising antivirals.
He is optimistic that the unprecedented amount of research going on in the world and the high level of cooperation 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 everything we put into clinical trials,” he said.
Remdesivir is one of many drugs being tested by the World Health Organization, comparing potential treatments for COVID-19 inpatients in a dozen countries, including Canada. Götte said we can expect major clinical trial results as early as April or May.
Götte said it was disappointing that the antivirals discovered during the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic – which could have been effective against COVID-19 as well – have never been translated into widely available treatments, largely because of the huge cost involved in developing new drugs.
“This time around, it is obvious that we have to cross the finish line,” he said.
“Ten billion dollars seems like a lot, a lot,” said Götte. “But in the context of this pandemic and the costs associated with this pandemic, that is nothing. “

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