New flu drug fights virus on two fronts

To ‘flu' now, and as the annual influenza vaccine season kicks off in countries like the UK as we head into winter, it’s timely that scientists have potentially stumbled on a new way to fight the flu. They’ve built a small, two-ended molecule that does two jobs: on the one hand it clogs up a key enzyme that flu viruses use to prune themselves free from the cells they infect so they’re able to spread. But once it’s done that, and glued itself to this flu enzyme, the molecule also acts as a homing beacon for the immune system, enabling white blood cells to flock to the site and assassinate infected cells. The findings have been published in the journal PNAS. Ed Hutchinson is a professor of molecular and cellular virology at the University of Glasgow, and he’s been taking a look at it for us…

Ed - This is a really exciting idea showing how in the future we might be able to take a new approach for treating influenza. This combines ideas both from drugs which can target the virus and also from vaccines which can get the immune system to fight back against the virus. This really combines the two. It takes an existing drug which binds to an enzyme called neuraminidase. The virus makes this neuraminidase to chew itself off cells. Its infected so it can get out of them. This drug mimics sugar and it gets into neuraminidase and it gums it up, stops it from working. We've known you can do that for a while. But what we authors realised is that also means that all of the neuraminidase proteins the virus has made, which are all over the infected cell, they're now labelled because they've got the drug stuck into them. So what they've also done is they've stuck something to the back end of that drug, which is recognised by the immune system. So now you haven't just gummed up one of the virus's enzymes and stopped them working. You've also put big come and get me signs all over the infected cell and the immune system comes in, kills the infected cell, takes out the virus. But importantly, it doesn't then cause lots of damage to the surrounding cells and it's immune damage, which tends to make us feel really sick when we're recovering from flu. It's a real surgical strike, which just takes out the infected cell that's there. And using experimentally infected mice, the authors have shown that it's incredibly effective in those mice at resolving really severe influenzas or infections.

Chris - To your knowledge Ed, will it work against or would you anticipate it will work against all the different types of flu? Because flu comes in a number of different flavours, doesn't it? There's animal flus like bird flu. There's human forms of flu and there are multiple forms of the human form of flu. So does this work against all of them?

Ed - That's a really important point, and what's really clever about this approach is that the drug mimics something which the viruses have to target to replicate inside their hosts. And because of that, any virus which grows well in humans should bind to the drug and therefore it should be labelled by this clever strategy and both drugged and attacked by the immune system at the same time, the authors of this paper have done a little bit of work to test that and their initial results in this paper look really promising. I think more work is needed to really show for sure that that's the case, but it really does show, I think, a lot of promise as something which could be really quite broadly protective.

Chris - Obviously this has been done in experimental animals. They used mice. Mice are not people. Would we anticipate that this would work equally well in a person?

Ed - There's lots of differences between mice and humans in general. Obviously if you've met a mouse you'll know that, but particularly when it comes to how they experience diseases like influenza. We start with mice because it is relatively easy to do experimental work on them. But things which are promising in mice do then need to be tested in other animals and ultimately in humans. And lots of things along the way we find unexpected reasons why they don't work as well as we'd hoped. So this isn't an absolute knockout and it's definitely going to get into humans tomorrow. All things being equal there's probably another five, ten years of work that's gonna be necessary to really test that unless there's some major crisis which forces people to develop influenza drugs quickly. But this is a really promising start for something which could be then taken further.

Chris - And could that major crisis be bird flu? Because we've been watching this very closely for the last couple of years and it's gone from lots of birds affected to now interesting things happening with cows and an ostensibly bird virus spreading through udders and milk in cows into calves. So it's sort of one step closer to us. Could this be a provoking factor to accelerate these trials?

Ed - To be very clear, we're not yet in a situation where H5N1 is spreading in humans, but it is something which we are looking at with a lot of concern. And if we think back to the last time there was a pandemic during SARS-CoV-2, people did start to develop drugs a lot more quickly than normal then because there was a massive need. However, there is an important difference between influenza and SARS-CoV-2, which is that influenza has been around for ages and actually in recent years there've been multiple new classes of influenza drug developed. So we already have quite a good arsenal of influenza drugs ready to go. If a crisis arose, a new one would certainly be valuable. And I think this could be a really useful addition to that. But it's not like the situation with SARS-CoV-2 where we were really starting from a cold start and needed to develop drugs when we had none at all to begin with.