There’s a paper out in Nature that’s gotten a lot of attention, because it’s directed towards therapies against Zika virus infection. The authors (a multi-center team) screening a library of existing drugs, known active pharmacological agents and tools, clinical candidates, etc. in a caspase-3 assay, since they’d recently found that zika infection in the CNS activates the caspase system.
Not surprisingly, they turned up emricasan, a known caspase inhibitor that’s been in the clinic in trials against chronic liver disease. Niclosamide was another hit, an old antihelminthic compound that’s still in use, although its side effect profile limits how often it’s used compared to alternatives. A third compound, PHA-690509, also showed efficacy – it’s a CDK inhibitor that’s been as far as Phase I, from what I can see. A number of other CDK-active compounds were also hits, which does point to it being involved in the infection process.
I think that the main value of these screens is often to point out mechanistic details like this – the drugs involved are being used as chemical probes, since their actions in cell assays and in vivo are fairly well worked out. (It’s for sure, though, that not every marketed drug is suitable for use as a probe – some of them hit a whole range of targets simultaneously). If an actual drug on the market hits (as niclosamide did here), that would speed up the possibility for its use against Zika infection, but it’s still something that would have to be taken through animal efficacy studies and human trials. In vitro screens are where most drugs get their start, for sure, but an awful lot (and I mean literally awful) never get much further.
This is all to say that the headlines generated by this work in the press (“Known drugs could cure Zika”) are way premature. The paper itself makes sure to say that further animal studies would be needed before you could even start talking about a human therapy, but that doesn’t make for such a great headline. It’s certainly a jump-start compared to a completely new compound, but it’s a lot further away than people might think. It takes time to set up a trial, to get the patients, and to figure out what happened once the dosing has finished, and none of this fits very well into the sort of dramatic narrative that the newspaper business would like.