A cure for the common cold?

Matt Woodley

17/09/2019 3:30:37 PM

Researchers claim to have found a way to protect against the world’s most common infectious illness.

Boy with cold-like symptoms.
Common colds may be a thing of the past, should the research prove successful.

Using CRISPR technology, the research team from Stanford University identified a single, apparently non-critical protein – methyltransferase SETD3 – that allows a broad range of enteroviruses, including rhinoviruses, to replicate and spread.
Instead of targeting the rhinovirus – which has approximately 160 different forms and mutates easily – the researchers, led by Associate Professor Jan Carette, used this information to ‘switch off’ SETD3, making the cells inhospitable for them.
Professor Jose Valladangos from the Peter Doherty and Bio21 institutes at the University of Melbourne, told newsGP the study’s results are ‘fascinating’ and could eventually lead to a drug that prevents the common cold.
‘Such a drug would be an effective antiviral that you could take as soon as you start developing symptoms,’ he said.
However, he added the research is still in its infancy and more work is needed before clinical trials or a market listing is even considered.
Professor in Microbiology and Molecular Biology at the University of New South Wales, Peter White, told newsGP the next phase would be developing the drugs that target SETD3 or its function.
‘Initial work would likely continue in mice using HTS [high-throughput screening] drug discovery approaches before possible pre-clinical safety studies,’ he said.
‘Targeting a host protein to prevent viral replication does not come without its dangers. Potential drug candidates that target host proteins are often more susceptible to adverse side-effects compared with drugs that target the virus directly.
‘One needs to look at what the function of the host protein is and then explore the possible outcome to the host if this function is modified or lost.’
Encouragingly, researchers have already genetically modified mice that were completely unable to produce the SETD3 protein, without apparent side effects.
‘Lacking that gene protected the mice completely from viral infection,’ Associate Professor Carette told the BBC.
‘These mice would always die [without the mutation], but they survived and we saw a very strong reduction in viral replication and very strong protection.’
The researchers also observed a 1000-fold reduction in a measure of viral replication inside human cells lacking SETD3, compared with controls. Knocking out SETD3 function in human bronchial epithelial cells infected with various rhinoviruses cut replication about 100-fold.
However, exactly what role the protein plays in the viral replication remains uncertain, and will require further research.
Professor Villadangos said one possible approach to determining the potential side-effects of ‘switching off’ SETD3 would be to search public databases for people with mutations in the gene in an attempt to determine whether these individuals are susceptible to viral infections.
If this approach fails, the next step would be to generate crystal structures of SETD3 bound to the viral partner proteins, in order to identify the region in both molecules that facilitates the interaction.
‘The two proteins would be produced with recombinant DNA technology and production, and [be] incubated together to form crystals that would then be analysed by X-ray diffraction in a synchrotron,’ Professor Villadangos said.
‘[The next step would be to] design and produce synthetic compounds that bind to SETD3 and prevent the viral proteins from binding to those same sites … [then] test the drug in animal models and eventually clinical trials.’
Scientists have already learned that enteroviruses have no use for the section of SETD3 that cells employ for routine enzymatic activity. Instead, enteroviruses carry a protein whose interaction with a different part of the SETD3 molecule is necessary for their replication.
‘This gives us hope that we can develop a drug with broad antiviral activity against not only the common cold but maybe all enteroviruses, without even disturbing SETD3’s regular function in our cells,’ Associate Professor Carette said.
‘We have identified a fantastic target that all enteroviruses and rhinoviruses require and depend on. Take that away and the virus really has no chance.
‘I think development can go relatively quickly.’

common cold CRISPR polio research

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