With a fast-moving epidemic like Ebola, doctors need to make use of every tool at their disposal. This includes giving a second life to already-approved drugs.
All with the hope of speeding up the discovery of new treatments for infected patients, people exposed to the virus, and healthcare workers in the middle of the crisis.
One research team is hoping to ease the epidemic by shortening the lengthy drug development process.
Their approach? Sifting through hundreds of existing drugs and other compounds for ones that might work against the Ebola virus. One of those potential treatments is the antidepressant Zoloft.
The researchers’ findings are published today in Science Translational Medicine.
Testing Hundreds of Potential Drugs
The researchers started with a collection of 2,600 compounds, including ones already approved by the Food and Drug Administration (FDA). They screened these to find the ones most likely to be effective in preventing infection by the Ebola virus.
This library contained “greater than 90 percent of the [FDA-approved] drugs available,” said study coauthor and virologist Gene Olinger, Ph.D., of the National Institute of Allergy and Infectious Diseases. “This screen also included some molecular probes and even common food additives and herbal compounds with reported anti-infective efficacy.”
From this collection, they identified 30 compounds with antiviral activity. The researchers tested the ability of these to kill the Ebola virus in cell culture.
Additional screening narrowed the list down to two potential drug candidates: Bepridil, a calcium channel blocker used to treat heart disease, and sertraline, an antidepressant more commonly known as Zoloft.
Both drugs are already approved by the FDA, although not for use against the Ebola virus.
“These drugs offer potential for repurposing for Ebola virus disease, either as single agents or in combinations, and could be used in circumstances similar to the current epidemic,” the authors wrote.
Two Drugs Prevent Ebola Infection in Mice
Further testing showed that these two drugs protected mice from Ebola infection. The compounds worked by preventing the virus from entering the cells of the mice, a key stage in the infection process.
Although both drugs improved the survival of mice after Ebola infection, additional research is needed to determine if they will work just as well in people.
“We plan to perform testing in rodents and nonhuman primates of both single and combinations [of the drugs],” said Olinger.
In some cases, using two drugs at the same time may be more effective in preventing Ebola. Drug cocktails may also allow doctors to use lower doses of the individual drugs to treat patients, which can sometimes reduce the side effects.
“A combination approach could be more valuable once disease occurs,” said Olinger. Single drugs, though, may be more appropriate after exposure — but before symptoms appear — “in preventing infection or stopping the early phase of disease.”
Drug Repurposing Saves Time and Money
Other research has looked at repurposing existing drugs to fight Ebola infection. In a study published in 2014 in Emerging Microbes & Infections, researchers identified 53 compounds that might work to prevent the Ebola virus from entering cells.
This approach to identifying new treatments for diseases has many selling points. But two of the main ones are speed and cost. These factors are especially critical during crises like the Ebola epidemic. After the first case appeared in 2014, the virus quickly spread throughout West Africa.
According to the World Health Organization, as of May 24, there have been more than 27,000 reported cases of Ebola virus in Guinea, Liberia, and Sierra Leone.
“Time, more than cost, is a key issue in Ebola. The current outbreak taught us this lesson the hard way,” Dr. Rajesh Gupta, an adjunct affiliate with the Center for Health Policy at Stanford University — who was not affiliated with the study — said in an email.
According to the National Center for Advancing Translational Sciences, it can take more than 14 years to move a new compound through the complicated process of turning it into an approved drug.
Drugs that are already approved by the FDA are several steps ahead.
“A repurposed drug will generally have a lot of the critical safety data already generated,” said Gupta. “All the standard animal and human toxicity studies along with robust data of real-world, in-human use will be available.”
Researchers Openly Share Findings
The benefits of the current study, however, go beyond the two drugs that were identified as potential treatment options for Ebola.
“We hope by making the drug screening data available, others will participate in this effort, as there were greater than 40 active compounds of interest,” said Olinger. “It may also spur interest with similar drugs being developed that may have similar mechanisms of action or chemical structures.”
The researchers also identified compounds that were ineffective against Ebola. This information will help other research teams avoid looking at them again in future studies.
Many potential vaccines and drugs for use against Ebola are currently being investigated. So far, none have been approved. Drug repurposing may enable researchers to fill the treatment gap left by the traditional way of developing new drugs.
This is essential for stemming the tide of the current Ebola crisis. But this approach is also an important tool to keep at the ready for future epidemics.
“As the recent outbreak indicated,” said Gupta, “if we keep taking the same approach to drug development, we’ll be consistently behind the curve of being able to evaluate a larger group of candidate therapeutics.”