People infected with Ebola might one day find themselves treating the virus with drugs originally intended to tackle depression and heart disease. By screening more than 2,500 existing drugs, scientists have identified 30 FDA-approved drugs that appeared to kill the Ebola virus in cultured cells. Among then, the antidepressant Zoloft and heart disease drug Vascor were able to stop the virus from reproducing in rodents as well. The findings, published today in Science Translation Medicine, are tentative but also encouraging. Developing new drugs takes a lot of time and money, and repurposing old ones that are already approved by the FDA could really speed things up.
70 percent of the mice on Zoloft survivedThe current epidemic in West Africa is the largest on record. Since its beginning, more than 27,100 people have been infected, causing about 11,100 deaths. There is no approved drug for Ebola right now, so researchers have tried to develop new treatments and vaccines to fight the outbreak — as well as future ones. But some have turned to investigating older ones that are intended for other purposes. These drugs "are ideal since they have known clinical data and safety profiles in humans," explains Gene Olinger, a virologist at the US Army Medical Research Institute of Infectious Diseases, and a co-author of the study.
To find out if existing drugs could be used against Ebola, Olinger and his team of researchers screened thousands of drugs against cells that had been infected with Ebola. Out of the lot, 30 drugs were able to kill the Ebola virus in a cell culture. But two drugs, drugs known as Zoloft and Vascor, were the most promising. They block the virus's ability to enter, replicate in, and exit infected cells. To further investigate the two drugs, researchers tested them in rodents. Both were able to protect mice from Ebola. About 70 percent of mice treated with Zoloft survived, whereas all the mice that were given Vascor survived.
"The findings are interesting, but without an evaluation of these most promising drugs in the nonhuman primate model it is hard to make much of it," says Thomas Geisbert, an immunologist at the University of Texas who didn’t participate in the work. The science behind the study is sound and the researchers are "good scientists," he told The Verge in an email, but finding a drug that works against Ebola in humans is "no small task."
"The odds of finding anything as efficacious as ZMapp or TKM-Ebola are very remote.""I and others have shelves and shelves full of things that show some in vitro activity against Ebola and of those, there are dozens or so that can protect mice," Geisbert says. Unfortunately, of all the drugs that protect rodents, ZMapp and TKM-Ebola are the only ones that work well in nonhuman primates so far. "Given the number of drugs that have been screened for Ebola over the years, the odds of finding anything as efficacious as ZMapp or TKM-Ebola are very remote."
Olinger and his team already have plans to try the drugs in larger animals. They also want to try using Zoloft and Vascor in combination with other drugs. "Viruses are often difficult to stop," so an approach that combines different drugs might be more effective, Olinger says.
Drugs take 10 years and "more than a billion dollars to develop."Emerging pathogens, especially viruses, are a threat to humans and animals — and researchers have few drugs to offer the clinicians that treat them, Olinger says. Drugs that have already been approved for use in humans therefore present an opportunity. If they can be repurposed during emergencies, scientists might be able to tip the balance in our favor. "This is especially important given that drugs typically take 10 years and more than a billion dollars to develop," Olinger says. It’s the kind of approach that can provide solutions while researchers work toward finding new, better drugs.
"We hope that [this study], including sharing our whole data set, will spur and incentivize our colleagues to consider these drugs" so that they can be used in future outbreaks, Olinger says. Of course, governments and health organizations will have to invest in basic and applied research if they want that approach to work. Doing so "remains critical link to timely and cost-effective medical treatments," he says.