It’s the “one drug right now that we think may have real efficacy” against COVID-19, according to World Health Organization officials. Two patients “near death” who recently took an experimental dose made remarkable recoveries. But it’s not the overhyped antimalaria drug being pushed by President Trump.
Remdesivir started out with similar hopes as a tool many thought could be effective against Ebola, the virus that caused another lethal epidemic in Africa six years ago. Now, scientists are rushing to find out whether or not the antiviral developed by Gilead Sciences can help fight the coronavirus. So what’s remdesivir? Who’s testing it? And how does it operate?
Welcome to Rabbit Hole, where we dive deep on the biggest story. It's for Beast Inside members only. Join up today.
ADVERTISEMENT
Who’s testing it?
We don’t have any evidence yet that remdesivir is effective against COVID-19 and for that, we need clinical trials in humans. Early on in the outbreak, a handful of institutions stepped up to announce new studies of the drug.
In February, the National Institutes of Health (NIH) in partnership with the University of Nebraska announced a randomized, controlled clinical study of remdesivir that aims to enroll 440 participants at 37 different locations across the country. The study is aimed at seeing how the drug helps patients who have relatively more severe cases of COVID-19 than those with just mild symptoms. To qualify, participants need to have tested positive for COVID-19 and show signs that the disease has affected their lungs, as evidenced in chest X-rays or other signs of respiratory issues.
Participants in the study either receive a placebo or a 10-day dose of the drug as researchers monitor their symptoms and vital signs and repeatedly test them for COVID-19.
At least two of the patients involved in the NIH study were part of a group of 14 Americans (with an average age of 75) who tested positive for coronavirus aboard the Diamond Princess cruise ship, which had docked in Japan. The NIH characterized the patients as “near death,” but all of them survived after receiving the drug, an outcome that the Institutes called “amazing.” Still, the survival of those patients remains little more than a welcome anecdote and far short of proof that the drug itself was responsible for their recovery.
Gilead Sciences, which makes remdesivir, has also announced two studies of the drug against COVID-19 and aims to recruit over 1,000 participants from Asia to participate in its trial.
Why remdesivir?
So why are researchers now looking at an Ebola drug to treat the coronavirus?
Antiviral drugs like lopinavir, ritonavir, and even drugs with antiviral properties like hydroxychloroquine have received the most interest since the outbreak. Remdesivir is getting attention in part because it has shown some preclinical success against COVID-19’s cousins.
Scientists had already conducted some research on remdesivir against other members of the coronavirus family, like the Middle East Respiratory Syndrome, which broke out in 2012, and the Severe Acute Respiratory Syndrome responsible for a 2003 epidemic in East Asia.
Studies that took place in labs and on mice and Rhesus macaques found some promise that the drug could stop the viruses from replicating. Those kinds of studies fall short of the randomized human clinical trials that offer the best data about a drug’s safety and efficacy, but the previous research was enough to pique scientific interest in remdesivir’s performance in humans.
Is there going to be a run on remdesivir now? We’ve seen the same pattern play out with a number of drugs that seem promising but remain unproven as weapons against COVID-19—a combination of fear, hope, and excess enthusiasm creates a demand that puts a run on supplies.
Many have rushed to secure supplies of drugs like hydroxychloroquine, which President Trump has promoted beyond any actual scientific evidence. Many have rushed to take the drug themselves absent a valid medical reason, a practice that is reckless and dangerous. That’s unlikely to happen with remdesivir, which has to be administered intravenously.
Its availability is also closely controlled now. When the COVID-19 pandemic began, Gilead Sciences, which makes the drug, made remdesivir available to patients infected with the virus on a compassionate-use basis, which allows severely ill patients to skirt some FDA regulations and receive unapproved drugs when they’re severely ill. Even under that limited exemption, Gilead still had to pull back and announce that “due to overwhelming demand” it would only make remdesivir available to pregnant women and children who had tested positive and were severely ill in order to preserve supplies.
How does it work?
We don’t yet know if remdesivir is effective against COVID-19, but we do know how it works against viruses like Ebola.
Remdesivir works by effectively sneaking a chemical wrench into your cells that sticks in the gears the Ebola virus uses to replicate itself.
“When a virus infects you, the infection starts off as just a few copies of the virus and it needs to make more copies very quickly so that it can launch an attack on the host. Whereas most of our cells divide only once every several days, the viral cells want to divide very rapidly. For any cell to undergo division, it has to take all this genetic material—either DNA or RNA—and it needs to make a copy of that,” Jennifer Heemstra, an associate professor of chemistry at Emory University, explained.
Viruses like Ebola need to replicate quickly to spread. To do that, they rely on polymerase enzymes to type out the genetic code in their RNA, using nucleoside triphosphates.
“If you’re like me, the faster you start typing, the more errors you make and viruses are exactly like that, too,” said Heemstra. “In order to go really fast, they have to have enzymes that are willing to make some mistakes.”
And it’s those genetic mistakes that remdesivir capitalizes on to function, according to Heemstra. The drug sneaks new triphosphates into the cell that look like the ones the virus needs to repeat the genetic code in its RNA but are different. When the virus uses them to try and repeat its genetic code, “it stops that RNA chain from getting finished and you can’t create a new copy of the virus.”
Your own cells help in the process. “If you try to give someone a triphosphate as a drug, it won’t be able to get into the cells,” says Heemstra. “We always think of chemists as making our drugs but in this case, chemists make a prodrug. It gets into cells, and then your cells do the final two synthetic steps in making this drug inside of your cells.”
Where did it come from?
Remdesivir owes at least some of its existence to the U.S. Army. The Ebola outbreak that began in West Africa in 2014 killed over 11,000 people, terrified many, and kickstarted a host of research that eventually led to a vaccine.
Along the way, researchers explored a number of possible treatments for ebola, including remdesivir—back then known as “GS-5734.” The U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), the Army’s institute for studying infectious diseases and possible bioweapons, worked with Gilead Sciences, and the CDC to identify which compounds in Gilead’s library of over 1,000 compounds collected across previous antiviral research might be effective against Ebola.
Early preclinical research showed promise. In animal trials, all of the monkeys infected with Ebola survived after receiving remdesivir on the third day after infection. However, subsequent clinical studies of remdesivir in human trials found that other anti-Ebola drugs were more effective in saving those infected.
