Scientists Manage to Inhibit Ebola Reproduction in Lab

Whether they can create an affordable drug that works in people remains to be seen, but the new method halts all strains of ebola in their tracks

Campaign to stop ebola, Sierra Leone, January 15, 2016
Aurelie Marrier d'Unienville, AP

Scientists have managed to inhibit the reproduction of ebola virus in laboratory conditions. Whether the breakthrough can translate into an actual drug is an open question, but the good news is that if it can, the product is likely to work on all ebola strains and maybe on some other vicious viruses as well.

The team isn’t suggesting a cure, it’s suggesting a way to stop the virus, which causes a deadly hemorrhagic disease, from multiplying.

Like all viruses, ebola is incurable; no treatment exists. Doctors can only try to boost the patient’s immune system and hope this does the job. Also, like all viruses, ebola is a complete parasite. Other parasites may need the host to survive, but without a host, a viral particle might as well be a rock. Viruses are the only known form of life that cannot proliferate on their own. They depend on their hosts.

Instead of dividing into two, like bacteria or amoebae, viruses “hijack” host cells. They inject their genetic material into the cell and it take over. Instead of making whatever it needs to make, the cell becomes a virus factory creating new virus particles.

The current breakthrough is that scientists in Copenhagen have identified a human enzyme crucial to this hijacking quality by ebola. They have demonstrated that inhibiting an enzyme called PP2A-B56 stops ebola from proliferating, as reported in Molecular Cell.

“PP2A-B56 is an enzyme that is present in all human cells and is hijacked by the virus to promote its own transcription,” explains Prof. Jakob Nilsson of the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen. “Without it, the virus is not able to produce new copies of itself,” he told Haaretz.

Under normal (uninfected) conditions, PP2A-B56 is involved in regulating a number of our metabolic processes. In other words, we need this enzyme for our cells and bodies to function normally. But when we're infected, specifically inhibiting PP2A-B56 stops the cell from making more ebolas.

Right now the team has managed to inhibit PP2A-B56 using short protein chains called peptides, which presumably bind to the enzyme, gumming up its ability to function. The team is working on creating small molecules that could do the same, that could be taken as medicine to inhibit the ebola infection.

Risk and reward

One snag is that inhibiting PP2A-B56 sounds bad for us. “We do not know the exact effect on a live person when PP2A-B56 is inhibited,” Nilsson says.

On the upside is that – theoretically – this concept should work on all strains of ebola, because this mechanism they identified and targeted is present in all strains of the virus. Even better, the approach might work with another deadly hemorrhagic disease, caused by a virus called Marburg, which is very similar to ebola. “It is thus a possible general approach to inhibit all virus strains,” Nilsson says.

All this remains to be proved. Meanwhile, Nilsson stresses that if a working drug can be developed that targets our own protein, rather than a viral protein, this is good. Why? Because the development of resistance to the drug is less likely. (Why? Because resistance arises through mutation, and bacteria, viruses and other microscopic germs mutate like crazy – we all do, but these are very little creatures with very short life cycles. They mutate more per time unit.)

This file photo taken on November 07, 2014 shows an audience member photographing a slide showing the likeness of an Ebola virus during an Ebola safety presentation.
AFP

The bottom line is that, in the lab, scientists developed a way to stop ebola viruses from using our own cells to make more viruses. Their method might or might not work in people, and might or might not be as bad as the disease – there is no way to know yet. But it’s a bright ray of hope.

“We anticipate that there is a therapeutic window where we can slow down the virus without too many side effects on the body,” Nilsson says. 

Given that the drug doesn’t even exist yet, it’s early days to ask how it would be administered, but the theory of its economics is rendered interesting by the sheer terror the word “ebola” evokes.

The disease has a very high mortality rate. Some survive, but may retain viral particles in their bodily fluids including sperm, ocular fluid and breast milk, and suffer from persisting problems and remain marginalized by stigma.

Geographically, ebola has not spread beyond certain parts of Africa. But every self-respecting conspiracy theorist has worried about weaponized ebola. “There is of course a large market for anti-bioterrorism,” Nilsson says. “If the virus spreads to the Western world the market would of course change.”