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February 22, 2005
An Antiviral Example
I mentioned yesterday that sometimes you can find an antiviral target that doesn't depend on what the virus itself has to offer. As fate would have it, there are a few drugs coming along that use just such a mechanism against HIV.
They're based on their affinity toward a protein called CCR5, which sits straddling the outer membrane of some types of cells. It's one type of receptor protein, whose lot in life is to latch onto specific other molecules if and when they come by. Our lot in life in the drug industry is to make small molecules that bind to them - the various kinds of receptors are hugely important drug targets. (For those outside the field, briefly, part of a receptor stays on the outside of the cell membrane, and part of it loops to the inside. When a molecule binds to the outside loops, that binding event changes the shape of the whole protein and sets off a signaling cascade in the cell, which signals can be tied into just about every cell process you can think of.)
In the mid-1990s, studies on patients who appeared more naturally resistant to HIV showed that they had a mutated form of CCR5. It turned out that the receptor is one of the things that the virus uses to get into blood cells and infect them, but the mutated form didn't let HIV bind to it very well. That immediately led to the idea of blocking a normal patient's CCR5 with some small drug molecule - if the receptor were stopped up with that, maybe HIV wouldn't be able to bind to it, either.
This receptor-blocking idea is a favorite in drug research. It's usually a lot easier to gum up a receptor than it is to mimic the specific thing that turns it on. That's why everyone jumped on this idea so quickly. But "quick" is a relative term in the drug development world. I think that the relevant chemical series were found to bind to CCR5 somewhere around 1996 or 1997. The projects at the different companies took off from there - and here it is 2005, and we're starting to begin to talk about something getting close to being submitted for the FDA's consideration. The thing is, that's not a slow calendar at all. It's normal to fast, unfortunately for all of us.
Schering-Plough (whose preclinical research team included several former colleagues of mine), GSK, and Pfizer are in the lead in this area, with several other companies also taking a crack at it. Early clinical results were promising, and we should be hearing more soon. Here's hoping that they all work.
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