Antidepressant Zoloft Shows Promise in Treating Ebola

By K. N. Smith | June 3, 2015 1:11 pm

zoloft

The common antidepressant Zoloft may be an effective treatment for Ebola, according to a new study on mice. Researchers also found that the blood pressure medication Vascor showed promise against the disease. And because these medications already have FDA approval for other uses, they could be available much more quickly than new Ebola drugs.

Drug Shortcut

Under normal circumstances, developing a new drug and getting approval from the FDA can take ten to fifteen years and cost over a billion dollars. Hence the appeal of testing existing medications for new purposes. Drugs like Zoloft and Vascor, which have already been proven safe for people, could bypass in vitro studies, animal testing, and the first phase of clinical trials to go straight to final stage clinical trials.

Lead author Lisa Johansen and her colleagues started with a library of about 2,600 compounds, which they tested against Zaire ebolavirus in the lab. Over one hundred of the compounds showed activity against the virus; of those, 80 already had FDA approval for other uses.

Ultimately, based on cellular studies, the researchers selected four drugs to try on mice. They infected the mice with Ebola and then started treating them with the drugs an hour after exposure.

Two drugs performed especially well: Zoloft and Vascor. Thirty days after infection, 70 percent of the mice treated with Zoloft (chemical name sertraline) had survived, and all of the mice treated with Vascor (bepridil) were alive. All the control mice had died by day nine, the researchers report this week in Science Translational Medicine.

Blocking Infection

Sertraline is a type of antidepressant called a selective serotonin reuptake inhibitor. It works by blocking reuptake of a chemical in the brain called serotonin. Bepridil treats high blood pressure by keeping calcium from entering the cells that line blood vessel walls. That keeps the vessels relaxed, or dilated.

But something else happens when these drugs encounter Ebola. Both drugs seem to prevent the virus from fully entering host cells, though researchers aren’t sure yet exactly how they’re interfering with the process.

Viruses like Ebola get into host cells using the same pathways that cells use to bring in nutrients and push out waste. First, a protein on the virus binds with a receptor on the outside of the cell. In response, the cell membrane folds around the virus, wrapping it in a pocket called an endosome. The endosome then opens up to allow the virus into the cell.

Meanwhile, the virus has its own protective envelope. That envelope fuses with endosome and then opens up, releasing the virus’s deadly payload of RNA into the cell, where it takes over the cell’s functions and produces more virus particles.

This is where sertraline and bepridil step in, according to Johansen and her co-authors. Researchers think that these drugs prevent the viral envelope from fusing with the endosome, which means that the virus can’t release its RNA into the cell.

Trials Ahead?

Johansen and her colleagues haven’t yet approached the FDA for permission for a clinical trial, according to co-author Gene Olinger. He told Discover that the team is currently working toward pre-clinical assessments, and they’re also studying ways to combine the compounds to create something that’s even more active in fighting Ebola. “A disease as acute as Ebola requires strong activity and we hope to achieve better outcomes with combinations,” said Olinger.

It can be difficult to design clinical trials for a disease like Ebola, which occurs in rare but intense outbreaks. Drugs can only be tested during an outbreak, but in the midst of an outbreak, it can be difficult to decide how to allocate an experimental treatment or to obtain consent from patients often too sick to communicate effectively. Doctors have struggled with those issues during the West African outbreak, and as it seems to be winding down, they may pursue other routes.

“We all hope the outbreak is soon to be over, so we would rely on the animal models (rodent and nonhuman primate models) to obtain efficacy and safety data for consideration as a human use intervention,” said Olinger.

The goal, of course, is to be ready with an effective treatment when the next outbreak occurs.

 

 Image by milo tobin via Flickr

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  • http://www.mazepath.com/uncleal/qz4.htm Uncle Al

    developing a new drug and getting approval from the FDA can take ten to fifteen years and cost over a billion dollars. ” Using FDA-approved meds off-label against a highly communicable lethal disease with no alternative therapies exposes patients to unknown hazards. Requalify beginning with Clinical Phase 1 studies on prisoners. Bureaucracy feeds on paperwork nobody ever reads.

    Do we have dose-effect curves? Do we have a 3-D plot of dual drug administration? If they act by different mechanisms, then they should be synergistic, improving survival further. One wonders if isolation suit manufacturers are greasing FDA palms to reject the discovery because “more studies are needed.”

    • MildredCLewis

      45$/hour@discovermagazine

      >/

  • Opio Faegansen

    “Sertraline is a type of antidepressant called a selective serotonin reuptake inhibitor. It works by blocking reuptake of a chemical in the brain called serotonin. Bepridil treats high blood pressure by keeping calcium from entering the cells that line blood vessel walls. That keeps the vessels relaxed, or dilated.

    But something else happens when these drugs encounter Ebola. Both drugs seem to prevent the virus from fully entering host cells, though researchers aren’t sure yet exactly how they’re interfering with the process.”

    This should be disturbing news for anyone who relies on these SSRIs. The same mechanism is that prevents the virus from entering host cells could also be depriving those host cells of other valuable resources. I’m sure someone will take up a study to explore these mechanisms more fully.

  • jimbow

    from what i read these drug maybe a way to keep a person from getting it in the first place. but it looks like the drug companies want to make another drug from them so they can charge allot more from poor nations.

  • David Fedson

    A practical treatment for Ebola patients that could have been used in West Africa

    More than 11,000 people in West Africa have died as a result of the Ebola outbreak in West Africa. Aside from conventional supportive care, there has been no specific treatment available. In most treatment units, more than 50% of the patients have died. This needn’t have happened.

    Patients who die of Ebola have elevated plasma levels of pro-inflammatory cytokines and other biomarkers that are also seen in patients with sepsis. In sepsis patients, these findings are associated with endothelial dysfunction and the loss of endothelial barrier integrity. Careful studies of foreign healthcare workers who were infected with Ebola virus and evacuated from West Africa for medical care showed they had developed dramatic fluid losses and electrolyte abnormalities. This was due to a massive increase in vascular permeability, a direct effect of the loss of endothelial barrier integrity.

    Cardiovascular scientists have known for many years that several common drugs, among them statins and angiotensin receptor blockers, have the ability to stabilize or restore
    endothelial barrier integrity. Moreover, these drugs are safe when given to patients with acute critical illness, and clinical studies have suggested that they might improve survival in patients with sepsis, pneumonia and influenza. This past November, local physicians in Sierra Leone treated consecutively approximately 100 Ebola patients with a combination of atorvastatin (40 mg orally /day) and irbesartan (150 mg orally/day) [5]. Only two inadequately treated patients are known to have died. Unfortunately, there was no financial
    or logistical support to conduct a proper clinical trial, and health officials in Sierra Leone have refused to release information on the treatment experience. Nonetheless, letters and memoranda exchanged by these physicians provide good evidence that treatment brought about “remarkable improvement.”

    This approach to Ebola treatment has two advantages. First, it uses inexpensive generic drugs that are widely available in any country with a basic healthcare system. All physicians who treat patients with cardiovascular diseases are familiar with atorvastatin and irbesartan, and most have used them to treat their patients. A 10-day course of treatment for an individual patient would cost only a few dollars.

    Second, this strategy targets the host response to infection, not the Ebola virus itself. For this reason, these drugs might be used to treat patients with any form of acute infectious disease, including pandemic influenza, in which a failure to overcome endothelial dysfunction could lead to multi-organ failure and
    death.

    These hopeful findings in Ebola patients who were treated with atorvastatin and irbesartan need to be externally reviewed and validated. If cases of Ebola continue to occur in West Africa, this treatment strategy should be tested in a proper clinical trial. If
    convincingly shown to be effective, it would radically transform the management of Ebola patients.

    References
    1. Fedson DS, Opal SM. Can statins help treat Ebola? The New York Times, August 15, 2014.

    2. Enserink M. Debate erupts on ‘repurposed’ drugs for Ebola. Science 2014, 345: 718-9.

    3. Fedson DS. A practical treatment for patients with Ebola virus disease. J Infect Dis 2015; 211: 661-2. (published online on August 25, 2014)

    4. Fedson DS, Jacobson JR, Rordam OM, Opal SM. Treating the host response to Ebola virus disease with generic statins and angiotensin receptor blockers. mBio 2015. To be published.

    5. Fedson, DS, Rordam OM. Treating Ebola patients: a “bottom up” approach using generic statins and angiotensin receptor blockers. Int J Infect Dis 2015. To be published.

    6. Fedson DS. Immunomodulatory adjunctive treatment options for Ebola virus disease patients: another view. Intensive Care Med 2015. To be published.

    May 13, 2015

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