Outsmarting a virus AND anti-vaxers: New drug to fight measles

If we vaccinated everyone who could be medically vaccinated against measles, measles would be eradicated.

Though there are other measles-like viruses, humans are the only hosts for what we commonly refer to as 'measles'.

Use vaccines to cut humans out of the equation? Extinct virus.

Its that 'easy'.

Unfortunately, measles 'wants' to exist, and they have human hosts, anti-vaxers, to help it stay alive.

Wat do?

Invent a shelf-stable oral drug that slows down measles infections, thats wat do:

An Orally Available, Small-Molecule Polymerase Inhibitor Shows Efficacy Against a Lethal Morbillivirus Infection in a Large Animal Model

1-- They had a 'small molecule inhibitor' of the measles virus RNA-dependent RNA-polymerase. The virus needs to make RNA from RNA. Humans dont do that. Stop this enzyme, stop the virus.

2-- They tinkered with their small molecule inhibitor to make it a better drug-- available via oral dosing, easy(ish) to synthesize, low cytotoxicity (doesnt kill virus AND cells, eg bleach), etc. They called the tinkered drug ERDRP-0519.

3-- ERDRP-0519, in the lab, can stop lots of different kinds of measles isolated from people. It also worked well stopping canine distemper virus, a virus related to human measles.

4-- Canine distemper virus kills 100% of the ferrets it infects. 100%. If ERDRP-0519 can 'save' an infected ferret, odds are it would be great at stopping human measles in people (which isnt as aggressive in humans as canine distemper virus is in ferrets).

5-- They gave ferrets ERDRP-0519, then infected them with canine distemper. They also did the reverse-- infecting the ferrets, then giving them the drug. ALL of the ferrets given the drug first survived. 100% lethal infection became 0% lethal. The ferrets who were infected first did not survive, BUT, they did survive 28 days, while the ferrets who did not get the drug only survived 14 days.

 

So, pre-exposure ERDRP-0519 can protect 100% of the ferrets. In the case of humans, that would be useful for people with known immune deficiencies at risk of exposure.

The more common situation would be a human unknowingly/finding out they were in contact with an infectious individual. They would be exposed before they would think to take the medication. Virus-->drug. In this case with the animal model, 100% of the ferrets died.

Total failure then?

Not necessarily. You need to remember the CDV-ferret model is a Worst Case Scenario scenario. 100% of infected ferrets die, where this is NOT the case with humans and measles. What they found in the infected-->drug ferrets is that their viral loads were still much lower than what they found in straight infected ferrets. In humans, this would likely translate to a) less pathogenic infection and b) less likely to transmit the virus to others.

While Im sure the researchers would have loved to see their drug protect ALL of the ferrets, the data they got is still extremely promising. If this translates into humans, we might have a way to treat vaccinated-but-unprotected individuals who are infected by anti-vaxers, and we might be able to stop anti-vaxers from infecting more people.

We might be able to eradicate this bastard!

BUT!

BUUUUUUUT!

The virus CAN evolve resistance to the drug. It can. They showed it in this paper. This drug is not perfect. But this drug could give us an edge over measles and the anti-vaxers who try to keep this disease alive.

More like this

> Humans dont do that.

When you say "humans" do you include the organisms that we can't live without? I know about the gut bacteria; don't know if there are any viruses that are equally at home inside us.

By Hank Roberts (not verified) on 29 Apr 2014 #permalink

Good question.... As far as we know, Hank, we don't harbour a lot of "good" viruses the way we do "good" bacteria. However, if we do, the advantage (and challenge) with a lot of antiviral drugs is that they are very specific to the targeted virus; we don't really have any "broad-spectrum" antiviral drugs the way we do antibiotics, mostly because every group of viruses presents a limited number of targets (they have a lot fewer proteins and processes of their own, since they use our cells' machinery for most things), and most of those are drastically different than targets in any other group of viruses.

....There is some evidence that some of the herpesviruses that infect most of us can be beneficial, but the jury is still out as to whether it's worth the associate complications (like cold sores and genital herpes, as well as things like cancer from Epstein-Barr Virus, another member of the Herpesvirdae family). Those are also DNA viruses and will be completely unaffected by any drug that we use to take down an RNA virus like measles.

It would be a great brake-trough if they can prove that the drug could fight measles effectively after the 'problem factors' named in the above can be solved.

In the experiments done till now it is not yet clear if the drug will be an asset to human kind in the future.

My concern is: Is it ethically correct to test this drug on animals? Is the similarity between ferrets-experiments and people big enough that the results in the experiments in the ferrets can be used without concern to base your conclusion about the effect of the drug on humans?

Would it be more efficient and accurate if you test the drug on the new developed bio-chips?
Here is a very interesting and informative TED-talk on the Bio-chips: http://www.ted.com/talks/geraldine_hamilton_body_parts_on_a_chip#t-16364
This shed a light to me on an unknown subject I knew nothing about. I think it can be of help to you.

I hope you see my comment in a positive light. Thank you.

By S. Harris u14104492 (not verified) on 29 Apr 2014 #permalink

Excellent news! If I understand this correctly, the implications of the data are that the drug could be developed for use a) as a kind of short term vaccine-substitute for people who are medically unable to get regular vaxes e.g. compromised immune system etc. (for example during outbreaks), and also b) as a post-infection treatment for measles patients to reduce their degree of infectivity to others. Is that approximately right?

Great phrasing, "...the anti-vaxers who try to keep [measles] alive." Exactly right.

Re. ferrets: Of course it's better to use biochips and similar technical advances, but it will take a while before these are developed to the point where the consensus of scientists is that they are a complete replacement for animal testing. Between now and then, the ethical requirement is to conduct essential projects in such a manner as to minimize the suffering of the animals.

This is very good news and a real breakthrough. It is amazing to think that scientists have come this far with their research of measles. Would it not be great if we can completely get rid of this virus for good?

But with every new brake-though, this one has its sets of obstacles, but if scientists can work on these obstacles and overcome them, they will have a great long term drug for fighting measles.
One of my concerns is also the animal testing. I do not feel that it is ethical to use these ferrets to test on and how do we know that the results found in the ferrets will be the results found in humans? I like the idea mentioned above about the bio-chips and I think this is a good way to stop animal testing.

I really liked reading this post and I learned a lot about something that I never really thought of.

By A. Kloppers 14006368 (not verified) on 30 Apr 2014 #permalink

When in the article it says that one of the issues is that the virus evolves resistance to the drug, does the virus evolve in such large increments that the drug becomes immediately resistant to the drug or in smaller increments where it takes a few mutations before it becomes resistant or with every mutation the drug begins to work a little less effectively?

By A. Karodia (14… (not verified) on 30 Apr 2014 #permalink

Wow this could be an amazing breakthrough to treat people who still suffer from diseases like measles especially those who are immune-deficient, giving better quality of life.

Superb discovery, this will truly help in curing measles,but total destruction of the disease will be best.

By Mlondolozi Inn… (not verified) on 01 May 2014 #permalink

Wow! That would be great breakthrough in medical science. My only worry is this: can the results on the ferrets be successfully translated to humans? Will humans react differently or will the results be practicalky the same? And also, will the drug, if it works and is released for use, be affordable to most peole? One must consider that most of the people that do not get vaccinated are people who cannot aford it.

By Yolanda botha … (not verified) on 04 May 2014 #permalink

It would be interesting to see if it can change the course of SSPE.