Why is it so hard to cure rabies?
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The short answer is because it can cross the blood-brain barrier.
In your head there’s a semi-permeable barrier that selectively allows certain necessary things to cross from the bloodstream to the brain’s cerebrospinal fluid. It’s a very selective barrier. Over 98% of our small molecule drugs can’t make it through this barrier which dramatically reduces our ability to find therapeutics which can do the job because what antiviral molecules we do have (and we have very few of them) are typically relatively huge compared to what can cross the BBB.
The rabies virus, however, can cross it. It does this by infecting the cells that make up the endothelium of the blood-brain barrier and then releasing the virus into the CSF on the other side of it. Once that happens death is almost certain since we don’t have any drugs that can get to the other side to help fight against it, even if we did have a drug with an anti-viral effect against rabies.
Why aren’t we looking for a drug with an anti-viral effect against rabies? Because a post-exposure rabies shot and/or human rabies immunoglobulin is almost 100% effective when given in a timely manner.
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