February 23, 2017

expert reaction to study looking at genome of human parechovirus (including the common cold)

Scientists publishing in Nature Communications claim to have identified – within the genome of Human Parechovirus – a “hidden code” of the common cold virus.

Prof. Peter Openshaw, Professor of Experimental Medicine at Imperial College London, and British Society for Immunology President, said:

“These are interesting but preliminary results from a good team of scientists, identifying a new possible approach to finding drugs that could be effective against a large group of viruses. It’s certainly a novel avenue to be explored, but a long way from finding cures for the common cold.

“The team looked at the structure of a specific virus (parechovirus) that is related to common cold viruses (rhinoviruses). They don’t know if their findings are applicable to all the related viruses. Even if their findings did apply to rhinoviruses (and it may not, as they say clearly in the paper), that’s a long way from getting an antiviral that works and is safe.

“Even if it were possible to get a safe and active drug, there are doubts about the use of antivirals once symptoms are present in short-term infections like colds. They might work in blocking the virus but not be so effective against the symptoms unless started very early- ideally before you even know the cold is brewing.

“So this is excellent science, but far from any practical application in the immediate future. It’s a great start, but it’s a long way from ‘cracking the Enigma code’ of the common cold.”

Prof. David Evans, Professor of Virology and Director, Biomedical Sciences Research Centre, University of St Andrews, said:

“This is fascinating science, building on the authors’ previous studies of plant viruses, that supports a new paradigm for how ‘packaging’ works in many small, medically important viruses. Packaging is the essential process of putting together the protein shell of the virus with its RNA genome. Without successful packaging no infectious virus can be made. The study convincingly demonstrates that the molecular signals that control the process are dispersed throughout the virus genome. This is markedly different from our previous understanding of the process in other viruses where individual, discrete signals are known to be sufficient. Scientifically it provides a whole new way to look at virus particle assembly and the results have fundamental implications for the way these viruses evolve.

“However, these types of viruses have outwitted our best efforts to make selective, non-toxic, effective antiviral drugs for at least three decades. Much more work will be needed to determine whether the packaging process is the Achilles’ heel of the common cold virus, a close relative of the virus used in this study. Several important questions remain. Are the signals conserved or different between the many hundreds of different strains of common cold virus? Does the presence of multiple signals mean all must be blocked or just some of them? These are not trivial things to work out. Until they are, the best protection from the common cold is still regular handwashing and avoiding touching your face with your fingers.”

Prof. Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“This is an interesting piece of work – it suggests that throughout time this group of viruses, which includes many viruses that cause the common cold, have been using identical means to package their genetic material in the virus particle in readiness for the next cycle of infection.

“The authors hope that this structural conservation will prove to be an Achilles heel – one that new drugs might target in order to bring about a broad acting antiviral.

“This is indeed feasible, but of course, these viruses are adept at mutating – they are the archetypal shape-changers. Could the virus mutate and escape the effects any such drug? We don’t know this will happen for sure, so it is definitely something worth exploring further.”

Dr John Tregoning, Senior Lecturer in the Department of Medicine, Imperial College London, said:

“In summary, the paper itself is a well worked through piece of science.  But it has no immediate impact on the clinical course of disease: it suggests new directions to follow for new drugs, it does not develop or test those new drugs.

“The paper is a thorough investigation of the mechanism in which a particular virus (and related viruses in the same genus) replicates.  In the current study, the authors investigated how a group of viruses (called parechoviruses) package their genetic material in order to produce more offspring viruses.  The outside of viruses are made of repeat units, the simplest analogy is the hexagons that make a football.  These units (called coat proteins) then assemble to make the whole virus.  The authors show that the viral genetic material (made of RNA) sticks to the inside of the coat protein in a specific way.  If the interactions between the coat and the genes are disrupted, the virus is less infectious.  This insight might lead to new antiviral drugs which could disrupt how the virus replicates.

“However, viruses in different families are extremely different.  Influenza and RSV – both major causes of disease – are fundamentally different to parechovirus; their genes are not even made the same way.  This may affect whether a drug that works on one virus would work on another.  In terms of burden of disease, the virus being studied here (parechovirus), is actually low on the list of viruses that cause respiratory disease (colds) – it has less impact than influenza, rhinovirus, RSV or parainfluenza amongst others.  Therefore, even treating this one virus may not greatly reduce the overall burden of common colds.

“In the press release, the author is quoted as saying “The common cold infects more than two billion people annually, making it one of the most successful viral pathogens” – however, there is not one common cold virus, there are many, many different types of cold virus.  Another author is quoted as saying “Vaccines, although our best source of defence against polio at the moment, can result in the release of more virulent strains of the disease” – it’s very important to remember that vaccines work.  The polio vaccine is highly effective and has reduced the global burden of polio from an estimated 350 000 cases in 1998 to 37 in 2016, and there has only been one case of polio this year to date thanks to the polio vaccine.”

* ‘Genomic RNA folding mediates assembly of human parechovirus’ by Shabih Shakeel et al. will be published in Nature Communications on Thursday 23 February 2017.

Declared interests

Prof. Peter Openshaw: “Prof Peter Openshaw’s research is funded by the Wellcome Trust, the MRC, BBSRC and the European Union. He has received honoraria or consultancy fees from GSK, Janssen, and Mucosis BV.”

Prof. Jonathan Ball: “No conflicts.

None others received.