A cure for the common cold?

21 May 2018

Interview with 

Professor Roberto Solari, Imperial College London

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Each of us suffers about three “cold” virus infections every single year. They make us miserable, they spoil our holidays and they cost us time off work. And, sadly, there’s no cure - yet. But that might be about to change thanks to scientists at Imperial College who began by trying to develop drugs to fight malaria but accidentally along the way stumbled instead on a method to block the growth of rhinoviruses, which are the chief causes of colds. Their new agent temporarily deactivates an enzyme in human cells that these viruses use when they try to grow. Chris Smith spoke to Roberto Solari, who helped to invent it, asking Roberto firstly to explain what his group did...

Roberto - So we’ve been trying to find ways of nobbling or blocking the virus if you like. This is a very simple virus; it has a protein shell and it has genes inside that protein shell but, like all viruses, it can only make more copies of itself inside our own cells. So when the virus infects our cells, it hijacks our cellular machinery to make more copies of itself.

Back in the 80s it was known that related viruses, and that includes polio virus and foot and mouth virus, actually add a fat molecule onto their protein shell, and they use a host enzyme to add that fat molecule onto their protein shell. So we thought that making a drug that inhibited that enzyme might block the virus and that’s what effectively we’ve done.

Chris - Do you know why they add that fat molecule because the host factor that does that is called myristoyltransferase isn’t it?

Roberto - That’s right.

Chris - It’s an enzyme that basically takes the chuck of the virus coat that’s being built and add this extra molecule onto it, but why do the viruses do that?

Roberto - What we discovered is that if the virus can’t add the fat molecule, the coat protein doesn’t form properly. So the coat protein is made as a very large protein that gets clipped and the fat is required for that clipping of the coat protein, and if you can’t clip it, it actually doesn’t form a proper shell.

Chris - Hence, if you can come up with a way to, albeit temporarily, block that enzyme it should be possible to significantly disable the virus from its ability to grown inside a cell?

Roberto - And that’s exactly what we found. We take cells in culture, and we infect them with virus, and we add the drug, and then we measure growth of new viruses. And what we can see is when we infect human cells with the virus we can block that effect.

Chris - And to what extent is it blocked? As in, if you measure how much virus you would expect to come out, compared to how much does come out, what degree of knockdown do you get?

Roberto - I would say close to 100 percent. It’s very effective at inhibiting growth of the virus.

Chris - How do the cells that you treat with this compound fare? Do they tolerate it okay?

Roberto - For a couple of days they do. It is actually well tolerated and that’s going to be one of the key challenges going forward to take this from something that works in a laboratory to something that works in a clinic. We have to test the safety and toxicity of these molecules; that’s all going to happen in the pre-clinical development phase that we’re now entering.

Chris - I suppose with the viruses like rhinoviruses, which cause the common cold, they are really confined to the cells that line our nose and throat those infections aren’t they? So could you make an inhaled form that doesn’t affect the rest of the body and, therefore, you do have a prospect of minimising the side effects?

Roberto - That’s an excellent suggestion. So, there’s two things that will be in our favour. One is that the course of a viral infection tends to be rapid, it’s over in a couple of days. So this is not a drug that you would take for months, or years. And the other way of minimising any toxicity would be to deliver it to the nose, or the lungs, where the virus is, in fact, growing. So that we don’t have to expose the whole body to the drug. They would be the two ways we would seek to minimise any toxicity to the patient.

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