Canadian researcher demonstrates experimental drug's potency against COVID-19
April 15, 2020
University of Alberta virologist Dr. Matthias Gotte (PhD) has published two papers in the last two months that theoretically demonstrate the efficacy of the experimental coronavirus drug remdesivir against its viral target, which the World Health Organization has called the “most promising candidate” among potential therapies.
Developed during the Ebola outbreak in 2014 by the American pharmaceutical company Gilead Sciences in collaboration with the National Institutes of Health (NIH) and the U.S. Department of Defence, remdesivir was shown to be safe but ineffective for treating Ebola. As a broad-spectrum antiviral, however, remdesivir showed promise in treating COVID-19. Previous studies in animals had also shown that remdesivir is active against other coronaviruses, and that the likely enyzme it was targetting did not differ significantly with the SARS-CoV-2 virus.
On February 24, Gotte and coauthors published a paper in the Journal of Biological Chemistry showing that remdesivir ”potently inhibits” the enzyme that synthesizes the genome of the Middle East respiratory syndrome (MERS) coronavirus, a step toward demonstrating the drug’s ability to inhibit a similar enzyme in SARS-CoV-2. Called the polymerase, this enzyme has been a key focus of Gotte’s antiviral research for nearly three decades, first for HIV and then for Hepatitis C. “Pretty much every virus contains such a polymerase,” he told Research Money. “If you target the polymerase, the virus cannot survive because it cannot replicate.”
After the Ebola outbreak, Gotte’s lab began working to create a platform for generating synthetic polymerases for all the viruses on a WHO top ten list of viruses that could cause an epidemic, on which coronaviruses were listed. Once he obtained the genetic sequence for SARS-CoV-2, he was able to produce a synthetic version of its polymerase in the test tube, which is likely the same as the one in the virus. The polymerase mistakenly incorporates remdesivir and then the virus fails to replicate.
Shortly after demonstrating remdesivir’s effectiveness for preventing MERS from replicating, Gotte’s lab obtained “almost identical results” against the SARS-CoV-2 virus. A new paper published on April 13 showed that the drug is “highly effective in stopping the replication mechanism of the coronavirus that causes COVID-19.” The evidence qualifies remdesivir as a "direct-acting antiviral" against SARS-CoV-2 and justifies clinical trials, Gotte told Science Daily, though the laboratory results don’t guarantee the drug will work in humans.
In fact, clinical trials for remdesivir are already underway, but scientists are questioning the validity of early results. An initial set of clinical trial data was released on April 10. Of 53 severely ill coronavirus patients who received the drug on a compassionate use basis, 36 (68%) improved, and the death rate was slightly lower than it had been for severe cases in China. The lead author, Jonath Grier, director of hospital epidemiology at Cedars-Sinai Medical Center in Los Angeles, called the results “hopeful.”
However, the trial lacked a comparison group, and so scientists are questioning its validity. Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told the National Post that ”the data from this paper are almost uninterpretable”
"The results of this study are potentially interesting and need to be verified in randomized controlled trials," says Gotte. "In fact, the study helps to address important questions with respect to the design of future trials. If patients benefit from remdesivir, it will be important to understand exactly who will benefit and who may not benefit."