Is there treatment for Ebola?

ZMapp, Favipiravir, Antivirals, and hopefully more

Dr. Kent Brantly during a press conference announcing his release from Emory Hospital on August 21, 2014
Dr. Kent Brantly was the first human to receive the experimental serum known as ZMapp. Jessica McGowan/Getty Images News/Getty Images

The simple answer: we don't know, but we're hopeful.

Before Ebola spread in West Africa in 2013 to 2015, no treatment had ever been successfully tested in humans. Once the epidemic broke out, treatments were often given for compassionate are. Patients have received treatments and have improved. However, the number of patients has been small, multiple therapies sometimes used, and for ethical reasons there have not been placebo-controlled comparisons.

Treatments of patients associated with improvements have included: ZMapp, favipiravir, as well as blood from survivors. One study of TKM-Ebola failed to show any benefit. However, initially before the first supplies ran out, at least 10 people have received ZMapp in the US, Liberia, Spain, and UK. Only 2 died. At least one has received favipiravr (in France) and TKM (in US) and survived. Later patients have started Brincindofovir- one died. Still from this, it is hard to tell for some of these drugs without true randomized trials, whether the drug or good supportive care, made the difference.

Still, we are hopeful. The mortality rate of the strain of Ebola (EBOV, Zaire) that is spreading in West Africa is exceptionally high. It was initially thought to be as high as 80-90% (as seen in prior epidemics elsewhere). It appears to be 45-60% in West Africa. Good supportive care may reduce mortality to 1 in 3. It is also difficult to compare survival rates as there are often delays in seeking care or being transferred for care.

Problem is: the stocks of ZMapp ran out.

But now more is becoming available - but the urgency has passed.

The WHO (World Health Organization) and government agencies, including the US FDA (Federal Drug Administration), are supportive of compassionate use and testing of these drugs. However, without proof that a treatment is lifesaving, there is the concern that what may seem lifesaving may be harmful - or simply distract from lifesaving care.

So where does that leave us?

Convalescent Serum

First treatment attempts for Ebola started with transfusing blood from survivors to those infected to give antibodies to fight the virus. A researcher survived following an Ebola needlestick in 1976 (and an infected doctor in 2014) after a transfusion but it was unclear whether the serum helped. Later in 1995, 8 patients were given blood and 7 survived, when overall most (80%) died. Subsequent analysis, however, showed demonstrable no benefit of transfusions (survival increases as time since infection and initial outbreak passes). Nonetheless, the World Health Organization has expressed interest in researching transfusions, as survivors, unlike drugs, are produced by the epidemic (though blood banking may be limited).

Convalescent blood transfusions have been used in West Africa, as well as for at least three patients in the US.

Monoclonal Antibody

Antibodies, derived in the laboratory rather than from transfusions, have been the most promising treatment so far.  One medication, ZMapp from Mapp Biopharmaceutical, is a mix of 3 monoclonal (ie highly specific) humanized antibodies (against surface glycoproteins). The treatment, through 3 medication injections, appears well-tolerated. Unfortunately, drug stocks have run out, though mass drug production is planned (through tobacco plants that will grow the drug). The FDA has allowed use upon request of this otherwise untested drug for Ebola patients when available.

Antiviral medications

Drugs may also directly fight the virus. There are multiple antiviral drugs: TKM-Ebola (Tekmira Corporation), BCX4430, (Biocryst Corporation), AVI-7537 (Sarepta), Favipiravir (Fujifilms)

Some drugs do not seem to work. Trial of TKM-Ebola was stopped in June 2015 because it did not seem to be effective It had been hoped that by using a type of RNA (small interfering RNAs called siRNA) that can stop the virus from spreading. It uses double stranded RNA to stop the expression of genes for 3 Ebola proteins ( Zaire Ebola L polymerase, Viral Protein 24 (VP24), and  VP35). Lab and animal studies have been successful (including with a similar virus, Marburg). Concern for a dangerous immune response slowed further testing, but the FDA is now speeding this up. 

BCX4430 acts as a building block for DNA/RNA (adenosine nucleoside analog) stopping virus replication; it has been successful in a monkey trial. 401.

Favipiravir, a drug approved against influenza in Japan has been effective in animal models and has been offered as treatment for Ebola. The drug is apparently a nucleotide analog preventing continued viral replication.

Brincidofovir (BCV, CMX001) is no longer being trialed for Ebola. Research is now focused on other viruses, like Adenovirus and CMV.

In fact, BCV was developed for use with DNA viruses - CMV (Cytomegalovirus), Adenovirus. Ebola is an RNA virus, not a DNA virus. The drug becomes cidofovir inside of cells. This drug has been used successfully with CMV and other DNA viruses, like papillomaviruses. Cidofovir is a nucleotide analog; it mimics a DNA building block and interferes with DNA lengthening in DNA viruses. It has largely not been used in RNA viruses like Ebola. However, the company that makes Brincindofovir, Chimerix, report laboratory studies at CDC, NIH showed anti-Ebola activity, which was very welcome news as the drug has been used safely in people before, though its anti-Ebola activity has not been confirmed in animals or humans yet. It would be an oral antiviral, which given the risks of needles with Ebola, would be promising. (Brincindofovir includes a lipid, or fatty, portion tied to cidfovir, which allows the drug to be swallowed, not injected).

AVI-7537 uses a modified RNA molecule to also attack the VP24 protein.

Approved medications

The easiest way to treat Ebola would be to find a drug known to be safe that is effective against Ebola. Screening already approved drugs for anti-Ebola activity has identified Selective estrogen receptor modulators (SERMs), such as Clomiphene and Torimefene used for female fertility and breast cancer treatment, as potential treatments.

Other drugs are possible. Ebola affects the clotting cascade causing clots and then bleeding. A (new) drug potentially affecting clotting rNAPC2 was studied as well as a known drug, rhAPC (recombinant human activated Protein C) with some optimism. Likewise, Others argue for cholesterol-lowering drugs based on other infections. Likewise, interferon has been looked at for use in Ebola. One doctor has used an HIV drug, Lamivudine, a nucleoside analog, in Ebola patients which may lead to further study.

Fake Medications

The FDA has warned against the use of unapproved medications. Many drugs sound good - theoretically - but without testing, it is unclear whether they are helpful or harmful.


A vaccine to prevent infection would be ideal. There is now a vaccine that has been tested and appears effective.

Prior to the 2013-2015 epidemic, there had been vaccines that had been developed for Ebola, but were not sufficiently tested. One vaccine was in effect tested on one patient; it possibly helped after a researcher's 2009 Ebola needlestick. This vaccine, VSV vaccine (recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein) has been further tested in animal models (but not on any other humans) and has been shown to be effective even up to 24 hours after exposure. It was a VSV vaccine that was tested and shown to be apparently effective in Guinea.

Early in the epidemic, there were multiple groups and governments that worked towards testing and using vaccines. The Canadian government has offered to distribute the limited stocks available of this experimental vaccine. NIH had proposed to rapidly test another vaccine candidate. The Chinese government later in 2015 also began testing a vaccine, using an adenovirus-vector.

In the end, there may be multiple vaccines. Unfortunately, much of the testing will be too late to help thousands who died in 2013-2015. It is also more difficult to test vaccines when there are few infections.

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