Breaking Down Science, Step by Step

Can this experimental Flu drug stop the Ebola Outbreak?

As the Ebola outbreak rages on, another drug enters the ring. Can an Experimental Flu drug developed by Fujifilm bring this disease to a halt ?

This news comes with a seeming panic over the fact that ZMapp might not be all it's cracked up to be, and that it may not have had much to do with Dr Brantly and Ms Writebol's recovery as the fact they were already getting better when they received it. I'm not saying I told you so, but I did heavily hint this would happen in my own article on ZMapp.


So what the hell is this drug ?

The first thing you have to realise about this drug is that it wasn't designed for Ebola. No, wait, I'm not phrasing it right. it wasn't just developed for Ebola. It is just one drug that has been developed as part of a push to create Broad-Spectrum Antivirals.

For many years, we've had Broad Spectrum Antibiotics, that could more or less kill off all types of bacteria without causing harm to human cells. They are poisons specially made to target the internal cellular processes of bacteria, which are different enough from humans that they don't harm us when we take them.

Can you simplify it a bit for me ?

Imagine a mad scientist somehow fuses you to an angry wolf, and you need to kill it without killing yourself. Eat lots of dark chocolate, and watch as your wolf-half succumb to the effects of theobromine.


The same treatment would work if you wandered into a malfunctioning teleporter and got fused with an enraged cat. Chocolate is a "Broad-spectrum" treatment for accidentally getting biologically fused to your pet. See ? This article is just full of practical information you can use in your daily life.

The same theory applies for bacteria. They have different metabolisms, which means that some chemicals that aren't very harmful humans will be lethal for them. Since a lot of different bacteria have similar metabolisms, a drug that kills off one may also kill off lots of others.


So why not pull the same trick with Viruses ?

This is where things get tricky. The thing that makes viruses so much harder to develop drugs for is that they use your own body against you. Viruses invade host cells, and once inside, they hijack the biological processes that the host cell uses to keep itself alive, to make more viruses. Viruses just don't have many biological processes that are unique to them, making it very difficult to develop a "Broad spectrum" antiviral.


That hasn't stopped some research groups from trying, some with more convincing results than others.

So how does this Fujifilm Drug work?

Don't call it that, it sounds really lame. It's name is Favipiravir, and it exploits a major weakness of one particularly troublesome subset of viruses. These are the RNA viruses.


Unlike the vast majority of living things, these viruses use RNA as the basis for their genome, as opposed to DNA. This unique trait of the RNA viruses allows for them to be targeted by specific drugs that won't harm their human hosts.

Favipiravir targets this process in a clever way.

RNA is like DNA, it's made up of four nucleotide bases. Viruses have special enzymes called RNA polymerases that use these nucleotide bases to make up brand new RNA strands. This is where Favipiravir strikes.


Favipiravir mimics the structure of these bases, allowing them to be taken up by RNA polymerases. Just like the other nucleotides, it gets incorporated into the growing RNA strand. Unlike the other nucleotides, it brings everything to a grinding halt.

Favipiravir stops the viruses from replicating their genomes, which in turn stops them replicating, and brings the infection to a grinding halt.


Wait, human cells use RNA as well, won't there be bad side effects ?

Ah, the biology major is strong with this one. There's some justified fear that it could turn out like a drug called Ribavirin, which works in the same way and has this long list of horrible side effects.


So far, it looks like mammal cells are a lot more fussy about what they incorporate into their DNA strands than virus, and turn their nose up at Favipiravir, preventing it from causing any damage to human cells.

The Viral RNA polymerases on the other hand are designed for speed, not care, and gobble up favipiravir without even thinking.


So does it work?

The drug looked good in mouse studies for flu, and did better than other flu drugs out there on the market, working even after treatment was delayed after infection. In most mouse studies, researchers barely wait more than a day before treating an infection they've given to mice, partly for welfare reasons, and partly to give their drugs the best chance of working. So giving a delayed treatment really shows that researchers have confidence in their drug.


It's currently made it through phase 3 trials in Japan, although the only reports I found talk only about how safe Favipiravir is, and not about whether its effective. Even so, on the strength of this, the Japanese Health Ministry have approved it as a treatment for Flu.

That's great and all, but will it work against Ebola?

In theory, it should. Most virus RNA polymerases are similar enough that they are vulnerable to Favipiravir in the same way as Influenza.


There have been two published studies that have used it as a treatment against Ebola.

In the first study, they infected mice with Ebola, and then began treatment one hour after infection, and saved 6 out of 6 mice, compared to the untreated mice who ended up dead.


The second study used Zaire Ebola virus, and they waited 6 days after the infection had started to begin treatment. again, 5/5 mice survived treatment. But, if they started treatment just two days later, all the mice had passed the point of no return and died.

So the drug looks like it could be pretty promising against Ebola.

Unlike Zmapp, it's already been stockpiled in high quantities in preparation for the next flu season in Japan. So there is already enough to start a reasonable trial during this outbreak. It's currently going through the process of approval by the World Health Organization to be tested in this outbreak.


That's great ! We can finally conquer Ebola ! Woooo-

Whooa, I'm going to stop you there before you start your victory parade. Whilst the drug has already gone through safety testing in humans, there is no actual guarantee that it will work.


Whilst it looks promising in mice, there are a tonne of subtle differences between the mice tested in these experiments and humans, which could potentially become major sticking points in the field. The treatment window could turn out to be very different for humans. So we should be a little bit more cautious with our optimism.

Come on, it's still good news, right ?

If it works, yes. Until then, I reserve the right to be as skeptical as possible. If there's anything we've learned from ZMapp's disappointing performance, it's that we shouldn't get our cheerleading pom-poms out for any drug that hasn't been fully tested yet.


References/ Further Reading

Animal models for Ebola and Marburg virus infections

Post-exposure efficacy of Oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model


Dose-Finding Study of Favipiravir in the Treatment of Uncomplicated Influenza

Favipiravir (T-705), a novel viral RNA polymerase inhibitor

T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections


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