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  • Alex Cloherty

The host and the hijacker

Updated: Jun 8, 2020

Imagine you are an ancient Queen or King, protecting your territory from an invader. Your enemy is getting closer and closer, and is at your borders. You need to defend your lands, so you decide to draw up a defense strategy.

Together with your most trusted advisors, you decide to focus on two plans of action:

  1. To go on the offensive by sending your best warriors out to the lands of your enemy, and

  2. To sabotage and lay traps in the parts of your territory that you expect your enemies will come to first.

Well, this scenario isn't entirely fictional. It is analogous to a new rationale for treating infectious disease: combination host-directed and direct-acting therapies.

In the case of infectious disease, your body is your territory, and the nasty bacteria or virus is the invader. Of course, the first thing we think about if we think of war is offence. Grab the best bows and arrows and guns and whatever other pointy or blowing up things, ARGHHH! Or, analogously, target the viruses or bacteria directly, by treating with antivirals or antibiotics, which specifically kill the microbes without harming us. These compounds are our sharpshooters, our snipers, against the incoming microbial force.

But, just like in ancient warfare, the enemy army (it's just microscopic in this case) relies on the territory it is invading. Like the enemy army needs to plunder food and water from the occupied territory, the virus or bacterium needs to steal tools or nutrition from your body in order to replicate and have a 'successful' onslaught - successful from the microbe's perspective, that is.

It was the understanding of this that led scientists to start focusing on a new kind of therapy: host-directed therapy. And yes, you are the host.

I've already hinted at this concept while writing about the hepatitis C virus. Because this virus depends so thoroughly on the fat in host cells, eliminating fatty deposits in host cells actually prevents virus replication. In other words, if you sabotage the fat, you sabotage the virus. Of course, fat is also important to us, so we don't want to get rid of all the fat in all of our cells. But, if we can reduce fat in only some of our cells, or for a limited time, it could help us fight back against the virus.

In a nutshell, the idea behind host-directed therapy is exactly the same as the fictional King or Queen's strategy #2 above: sabotage and lay traps in the parts of your territory that you expect your enemies will come to first. Scientists are pretty good at figuring out which pieces of human (or animal, or plant, or whatever) cells that microbes rely on for their lifecycle. There are textbooks full of this stuff - trust me, I've read them. So, the new idea is, let's hit 'em where it hurts. If we cut off what they want from us, we won't look like such a desirable territory after all.

This way of thinking is also contributing to how scientists hope to target the novel coronavirus, at least in the shorter-term period before an effective vaccine is available. Many scientists are talking about combining host-directed strategies, like ACE2 blockers, with more traditional direct-acting antivirals. We hope that fighting back with two complementary strategies should give us the best chance at beating the bug.

In fact, the research group in which I am doing my PhD has just started working on a potential new line of host-directed drugs to use against the coronavirus. We spent a couple of hours today planning out all of our experiments for the next weeks, so that we can always keep 1.5 meters away from each other, and trade off who's in the lab when. We're all in this together.

Until next time,

~Alex

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