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 coding system 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.
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 virus assembly. 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 virus 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.
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.
Professor Stockley and Dr Tuma are available for interview. Please contact Chris Bunting, Senior Press Officer, University of Leeds; phone: +44 113 343 2049 or email email@example.com.
Professor Twarock and Dr Dykeman are available for interview. Please contact David Garner, Senior Press Officer, University of York; phone: +44 1904 322153 or email firstname.lastname@example.org.
The full paper: N. Patel et al. ‘Revealing the density of encoded functions in a viral RNA,’ PNAS (2014) is available to download (URL: www.pnas.org/cgi/doi/10.1073/pnas.1420812112; DOI 10.1073/ pnas.1420812112)
Helen Miller, Innovate UK (Apr 2018), £999,960
Elisabetta Groppelli, David Rowlands & Stanley Lemon (University of North Carolina), Medical Research Foundation Fellowship (Apr 2018), £293,494
Nikesh Patel, Medical Research Foundation fellowship (Apr 2018), £290,976
Jessica Kwok & Ralf Richter, Leverhulme Trust (Apr 2018), £298,273
Julie Aspden, Royal Society (Apr 2018), £20,000
Liz Duncan, Royal Society (Mar 2018), £14,602
Alex O'Neill & Ryan Seipke, BBSRC (Feb 2018), £45,489
Jim Deuchars, Royal Society (Feb 2018), £16,300
Stefan Kepinski & Netta Cohen, Leverhulme Trust (Feb 2018), £320,387
Lisa Collins, BBSRC (Feb 2018), £49,950
Lars Jeuken, BBSRC (Feb 2018), £30,000
Nikita Gamper, BBSRC (Feb 2018), £30,000
Alison Baker, BBSRC (Feb 2018), £30,000
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Jessica Kwok and Ronaldo Ichiyama, International Spinal Research Trust (Feb 2018), £94,450
Alex O'Neill, Oxford Drug Design (Jan 2018), £86,098
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Alison Baker, Yun Yung Gong and Lindsay Stringer and ICRISAT India, HEFCE GCRF Grant (Jan 2018), £27,000
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
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Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
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Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
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