Can Remdesivir Treat Both COVID-19 and Ebola?
‘Right now, the world is utterly focused on the coronavirus disease outbreak known as COVID-19. That’s certainly true for those of us at NIH,’ said Dr. Francis Collins.
On April 17, 2020, Dr. Collins posted this message. ‘Though I am working from home to adhere rigorously to physical distancing, I can’t remember ever working harder, trying to do everything I can to assist in the development of safe and effective treatments and vaccines.’
So let’s focus on an experimental anti-viral drug, called remdesivir, that was originally developed for the deadly Ebola virus.
Though remdesivir failed to help people with Ebola virus disease, encouraging results from studies of coronavirus-infected animals have prompted the launch of human clinical trials to see if this drug might fight SARS-CoV-2, the novel coronavirus that causes COVID-19.
You may wonder how a drug could possibly work for Ebola and SARS-CoV-2, since they are very different viruses that produce dramatically different symptoms in humans.
The commonality is that both viruses have genomes made of ribonucleic acid (RNA), which must be copied by an enzyme called RNA-dependent RNA polymerase for the virus to replicate.
Remdesivir has an affinity for attaching to this kind of polymerase because its structure is very similar to one of the RNA letters that make up the viral genome.
Due to this similarity, when an RNA virus attempts to replicate, its polymerase is tricked into incorporating remdesivir into its genome as a foreign nucleotide, or anomalous letter.
That undecipherable, extra letter brings the replication process to a crashing halt—and, without the ability to replicate, viruses can’t infect human cells.
Would this work on a SARS-CoV-2 infection in a living organism?
An important step was just posted as a preprint yesterday—a small study showed infusion of remdesivir was effective in limiting the severity of lung disease in rhesus macaques.
That’s encouraging news.
But the only sure way to find out if remdesivir will actually help humans who are infected with SARS-CoV-2 is to conduct a randomized, controlled clinical trial.
In late February, NIH’s National Institute of Allergy and Infectious Diseases (NIAID) did just that, when it launched a randomized, controlled clinical trial to test remdesivir in people with COVID-19.
The study, led by investigators at the University of Nebraska Medical Center, Omaha, has already enrolled 805 patients at 67 testing sites. Most sites are in the United States, but there are also some in Singapore, Japan, South Korea, Mexico, Spain, the United Kingdom, Denmark, Greece, and Germany.
All trial participants must have laboratory-confirmed COVID-19 infections and evidence of lung involvement, such as abnormal chest X-rays, rattling sounds when breathing (rales) with a need for supplemental oxygen, or a need for mechanical ventilation.
They are randomly assigned to receive either a round of treatment with remdesivir or a harmless placebo with no therapeutic effect.
To avoid bias from creeping into patient care, the study is double-blind, meaning neither the medical staff nor the participants know who is receiving remdesivir.
There is also an early hint from another publication that remdesivir may benefit some people with COVID-19.
Since the end of January 2020, Gilead has provided daily, intravenous infusions of the drug on a compassionate basis to more than 1,800 people hospitalized with advanced COVID-19 around the world. In a study of a subgroup of 53 compassionate-use patients with advanced complications of COVID-19, nearly two-thirds improved when given remdesivir for up to 10 days.
Most of the participants were men over age 60 with preexisting conditions that included hypertension, diabetes, high cholesterol, and asthma.
This may sound exciting, but these preliminary results, published in the New England Journal of Medicine, come with major caveats. There were no controls, participants were not randomized, and the study lacked other key features of the more rigorously designed NIH clinical trial.
In the meantime, basic researchers continue to learn more about remdesivir and its interaction with the novel SARS-CoV-2 coronavirus that causes COVID-19 disease.
Such detailed biochemical information will be vital in the weeks ahead, especially if data generated by the NIH clinical trial indicate that remdesivir is a worthwhile lead to pursue in our ongoing search for anti-viral drugs to combat the global COVID-19 pandemic.
This blog is written by Francis S. Collins, M.D., Ph.D., the 16th Director of NIH.
SARS-CoV-2 vaccine and treatment developments published by Precision Vaccnations.