The tools that exist for fuzzing speedruns (TASers call it "botting") are fairly primitive, excluding a few game-specific ones. Because of that, there really aren't that many TASes where a distributed randomised search could make improvements which don't get immediately overshadowed within a day of human attention. Improving botting tools and increasing their adoption would be more effective IMO. (Incidentally, TASVideos.org recently banned one of the people pioneering bot development.)

Meanwhile BOINC is well-established as the platform for distributed computation. If you can figure out how to squeeze its work units into Wasm challenges, I'm sure a lot of researchers would thank you.

Yeah, I'm using PoW-based "DDOS defense mechanism" for a current project and had this thought too. I briefly looked into what it would take to exploit PoW to do something economically valuable like folding@home, and it looked a bit tricky. At first glance, these sort of projects seem a bit unsuitable for real-time PoW because they were designed to be run on desktops and so tend to do things in large batches. There probably are other use-cases that could be more suitable though.

Might be worth chucking that thought into Astra, especially if someone springs the $$$ money for it?

This would be rad.