Scientists discover viral 'Enigma machine'

February 4, 2015, University of Leeds
A code hidden in the arrangement of the genetic information of single-stranded RNA viruses tells the virus how to pack itself within its outer shell of proteins.

Researchers have cracked a code that governs infections by a major group of viruses including the common cold and polio.

Until now, scientists had not noticed the code, which had been hidden in plain sight in the sequence of the ribonucleic acid (RNA) that makes up this type of viral genome. 

But a paper published in the Proceedings of the National Academy of Sciences (PNAS) Early Edition by a group from the University of Leeds and University of York unlocks its meaning and demonstrates that jamming the code can disrupt virus assembly. Stopping a virus assembling can stop it functioning and therefore prevent disease.

Professor Peter Stockley, Professor of Biological Chemistry in the University of Leeds' Faculty of Biological Sciences, who led the study, said: "If you think of this as molecular warfare, these are the encrypted signals that allow a virus to deploy itself effectively."

"Now, for this whole class of viruses, we have found the 'Enigma machine'—the that was hiding these signals from us. We have shown that not only can we read these messages but we can jam them and stop the virus' deployment."

Single-stranded RNA viruses are the simplest type of virus and were probably one of the earliest to evolve. However, they are still among the most potent and damaging of infectious pathogens.

Rhinovirus (which causes the common cold) accounts for more infections every year than all other infectious agents put together (about 1 billion cases), while emergent infections such as chikungunya and tick-borne encephalitis are from the same ancient family.

Other single-stranded RNA viruses include the hepatitis C virus, HIV and the winter vomiting bug norovirus.

This breakthrough was the result of three stages of research.

  • In 2012, researchers at the University of Leeds published the first observations at a single-molecule level of how the core of a single-stranded RNA virus packs itself into its outer shell—a remarkable process because the core must first be correctly folded to fit into the protective viral protein coat. The viruses solve this fiendish problem in milliseconds. The next challenge for researchers was to find out how the viruses did this.
  • University of York mathematicians Dr Eric Dykeman and Professor Reidun Twarock, working with the Leeds group, then devised mathematical algorithms to crack the code governing the process and built computer-based models of the coding system.
  • In this latest study, the two groups have unlocked the code. The group used single-molecule fluorescence spectroscopy to watch the codes being used by the satellite tobacco necrosis virus, a single stranded RNA plant virus.

Dr Roman Tuma, Reader in Biophysics at the University of Leeds, said: "We have understood for decades that the RNA carries the genetic messages that create viral proteins, but we didn't know that, hidden within the stream of letters we use to denote the genetic information, is a second code governing . It is like finding a secret message within an ordinary news report and then being able to crack the whole coding system behind it.

"This paper goes further: it also demonstrates that we could design molecules to interfere with the code, making it uninterpretable and effectively stopping the in its tracks."

Professor Reidun Twarock, of the University of York's Department of Mathematics, said: "The Enigma machine metaphor is apt. The first observations pointed to the existence of some sort of a coding system, so we set about deciphering the cryptic patterns underpinning it using novel, purpose designed computational approaches. We found multiple dispersed patterns working together in an incredibly intricate mechanism and we were eventually able to unpick those messages. We have now proved that those computer models work in real viral messages."

The next step will be to widen the study into animal viruses. The researchers believe that their combination of single-molecule detection capabilities and their computational models offers a novel route for drug discovery.

Explore further: Researchers take mathematical route to fighting viruses

More information: N. Patel et al. 'Revealing the density of encoded functions in a viral RNA,' PNAS (2014), http://www.pnas.org/cgi/doi/10.1073/pnas.1420812112 ; DOI: 10.1073/pnas.1420812112

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14 comments

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SoylentGrin
5 / 5 (6) Feb 04, 2015
It looks like it's not the cure for the common cold, but you can see it from here.

Disrupting single stranded RNA viruses is a huge discovery, but I'm concerned with what happened to DRACO, which promised to disrupt all viruses. Funding dried up, and the project is dangling looking for private donations.

If this leads to a cure for all rhinovirus (and other ss rna viruses), it would eliminate an entire industry. How much is made on cold remedies? Again, I think it will fall prey to there being less interest in curing something in favor of milking treatment instead.
NATO 7_62mm X 51mm
3.4 / 5 (5) Feb 04, 2015
I am in agreement with SoylentGrin. While this discovery could very likely lead to the elimination of many ailments mankind suffers from, the likelihood that this research will be buried or otherwise hindered from use due to existing industry economics is a real concern.
Torbjorn_Larsson_OM
4.4 / 5 (7) Feb 04, 2015
Conspiracy theories are not a "real concern" because 1) they lack data (on "hindered from use due to existing industry economics") and 2) they are the least likely prediction for anything (because they are constructed to lack data, e.g be non-testable, non-functional, ideas).
tonybudz
1 / 5 (5) Feb 04, 2015
To code is to code a code that encodes its code into another code, the question to the solution lies with the author of the code.
ron234
not rated yet Feb 04, 2015
The synergy here of researchers and mathematicians is outstanding. My first thought was to wonder what work remains to arrive at a cure(s). My second thought was in agreement with SoylentGrin and NATO that other agendas and existing industry economics might be the highest of any remaining hurdle.
rocket77777
not rated yet Feb 04, 2015
Fujifilm T-705 flu medicine Favipiravir/Avigan is a cure for ebola. Luckily, it was not greedy evil USA pharmaceuticals who would have made tiny non-beneficial modification and charge arm and leg. It works on other virus too so it is equivalent of penicillin for virus and should win nobel prize. It should also help with aids since even if it does not work for HIV directly, it will help with secondary virus diseases which attacks weakened immune system. Chinese government already stole and uses same drug without paying Fijifilms.

Avigan must be blocking this code.
animah
5 / 5 (1) Feb 04, 2015
it's not the cure for the common cold, but you can see it from here.

I'd be concerned with the high potential toxicity of molecules that interfere with genetic encoding though. Making them specific enough to only disrupt targeted organisms might take a number of years.

Also, one can only hope this technique does not lead to an entirely new class of biological warfare agents...
arpotu
5 / 5 (1) Feb 04, 2015
The Russian practice of using bacteriophage viruses rather than antibiotics is looking more and more rational every day.
dtxx
5 / 5 (4) Feb 04, 2015
If this leads to a cure for these viruses there is no way it's going to be buried by the cough syrup industry. What will take place is a patent race and war. Now that this information is public, the group that did the research are not the only ones who can use the concept to get the cure. It's sort of like how at the end of world war II the world had just come far enough that nukes were going to happen one way or another, nazis or us. So if you're the lab behind this, do you develop the cure and secure the market or do you let the other guy take his time, take your work, and make countless billions?

The conspiracies are insane because scientists, despite how much they seem to be derided on a goddamn science website of all places, do have morals. If I were involved in research and the boss came down and said hey we're gonna keep this secret and let millions of people keep dying to preserve a product line, I'd have no qualms risking my life or spending it behind bars to get it out.
Drexus
5 / 5 (1) Feb 05, 2015
While exciting this discovery may represent, there are valid concerns regarding influence from pharmaceutical corporations — not based on probability assessment verses the lack of data, but simply on the composite understanding in the voices shown here. We all know this story because we've seen similar episodes. Pharmaceuticals are not NPOs, and if you look at their legal and patent track record, we should know better than to kid ourselves.
kochevnik
3.7 / 5 (3) Feb 05, 2015
@TLOM Conspiracy theories are not a "real concern" because 1) they lack data (on "hindered from use due to existing industry economics") and 2) they are the least likely prediction for anything (because they are constructed to lack data, e.g be non-testable, non-functional, ideas).
Every war begins with a conspiracy. Conspiracy is a crime. You have been brainwashed
JVK
1 / 5 (2) Feb 05, 2015
See also: http://genomebiol...bstract/

"Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates. In some cases, critical amino acid substitutions have been identified that affect species-specific virulence [7-9]."

This links viral microRNAs to cell type differentiation across species via the biophysically constrained chemistry of RNA-mediated protein folding.
Whydening Gyre
4 / 5 (4) Feb 05, 2015
See also: http://genomebiol...bstract/

"Current efforts to understand the host-specificity of the virus have largely focused on the amino acid differences between avian and human isolates. In some cases, critical amino acid substitutions have been identified that affect species-specific virulence [7-9]."

This links viral microRNAs to cell type differentiation across species via the biophysically constrained chemistry of RNA-mediated protein folding.

Whatever the f*#% that meant....
Returners
3.7 / 5 (3) Feb 07, 2015
Consider the benefits to farming if you could eliminate problematic animal viruses. The increased productivity and quality of life would provide enormous economic value.

It is hard to imagine the benefits of eradicating all of those human illnesses and all livestock and pet illnesses of these families.

It would instantly get a top 10 scientific discoveries of all time, right next to fire, refrigeration, and the vaccine.

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