Mice infected with Ebola survived when treated with the prescription drugs Zoloft and Vascor, a small preliminary study has found. Although final results are still years away, if the drugs turn out to also be effective in humans it could mean new treatments for the deadly disease.
The Ebola virus has killed over 11,000 Africans in the still ongoing outbreak which started in December 2013.
In the preliminary study, researchers treated 10 mice infected with Ebola using Vascor (bepridil), which is prescribed to control blood pressure in heart patients. All treated mice survived the deadly virus.
Out of 10 infected mice treated with the antidepressant Zoloft (sertraline), seven survived. The next phase will be testing the drugs in guinea pigs and monkeys, said immunologist Gene Olinger.
Olinger, of Boston University’s National Emerging Infectious Diseases Laboratory (NEIDL), started workinh with Ebola and other viral hemorrhagic fevers (VHF) in 2004, when he was a civilian employee with the Army. NEIDL is waiting to be approved for Biosafety Level 4 research, which would include on-site, live-virus Ebola studies.
Olinger says his lab began to develop a drug screen using a live virus that might find an effective treatment. As such, it made sense to screen existing Food and Drug Administration–approved drugs, not just for the time saved, but because such a repurposing approach has been used in infectious diseases previsouly.
For example, Viagra was originally a heart treatment drug before its effectiveness against erectile dysfunction was discovered, and thalidomide, used for nausea in pregnant women until it was found to cause birth defects, is now seen as an effective cancer drug.
Zoloft and Vascor seem to work by blocking the cellular pathways Ebola enters through, findings which surprised Olinger.
“I was shocked at the breadth of the type of drugs that had an impact,” he says, meaning drugs blocking estrogen receptors in the cells. “Why would a virus need an estrogen receptor? I could see years of research just on a basic level just off that one finding.”
“We do know there are synergistic combinations that are possible,” Olinger concludes. The eventual therapy, in other words, might be a cocktail of several drugs, similar to the way HIV is treated.
Lisa M. Johansen, Lisa Evans DeWald, Charles J. Shoemaker, Benjamin G. Hoffstrom, Calli M. Lear-Rooney, Andrea Stossel, Elizabeth Nelson, Sue E. Delos, James A. Simmons, Jill M. Grenier, Laura T. Pierce, Hassan Pajouhesh, Joseph Lehár, Lisa E. Hensley, Pamela J. Glass, Judith M. White, Gene G. Olinger
A screen of approved drugs and molecular probes identifies therapeutics with anti–Ebola virus activity
Abstract:
“Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus.
Selective antiviral activity was found for 80 U.S. Food and Drug Administration–approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.”
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