05:46pm Wednesday 14 November 2018

Molecule that acts on human cells might provide hope for cold cure

Researchers have lab-tested a molecule that can combat the common cold virus by preventing it from hijacking human cells.

Early lab-based tests with human cells have shown the molecule’s ability to completely block multiple strains of cold virus, and the team hope to move to animal and then human trials.

The common cold is caused by a family of viruses with hundreds of variants, making it nearly impossible to become immune to or vaccinate against all of them. On top of that, the viruses evolve rapidly, meaning they can quickly gain resistance to drugs.

For these reasons, most cold remedies rely on treating the symptoms of the infection – such as runny nose, sore throat and fever – rather than tackling the virus itself.

However a new molecule, developed by a research team led from Imperial College London, and including experts from the University of York’s Structural Biology Laboratory, targets N-myristoyltransferase (NMT), a protein in human cells. Viruses ‘hijack’ NMT from human cells to construct the protein ‘shell’, or capsid, which protects the virus genome.

Evolve resistance

Dr Jim Brannigan, from the University of York’s Department of Chemistry, said: “All strains of the virus need this same human protein to make new copies of themselves, so the molecule should work against all of them. Additionally, the molecule also works against viruses related to the cold virus, such as polio and foot and mouth disease viruses.

“The drug inhibits a host protein so the virus cannot evade its force by mutation and is unable to evolve resistance.”

Lead researcher Professor Ed Tate, from Imperial College London, said: “The common cold is an inconvenience for most of us, but can cause serious complications in people with conditions like asthma and COPD. A drug like this could be extremely beneficial if given early in infection, and we are working on making a version that could be inhaled, so that it gets to the lungs quickly.”

Toxic side effect

There have been previous attempts to create drugs that target human cells rather than the viruses, but many have the side effect of being toxic. The researchers showed that the new molecule completely blocked several strains of virus without affecting human cells. Further study is needed to make sure it is not toxic in the body.

The team were originally looking for compounds that targeted the protein in malaria parasites. Screening large libraries of compounds, they found two hits and were surprised to discover that they worked best together.

Dr Brannigan said: “Visualising the precise interaction between the compounds and the target protein guided the design of very potent inhibitors, which are effective at low doses.”

More potent

By inventing a novel way to combine the two hits, the team created a molecule, code-named IMP-1088, which is more than a hundred times more potent than previous molecules targeting the protein in humans.

The results are published in the journal Nature Chemistry.

 

University of York 

 


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