Make it expensive to spam, the whole idea of Proof of work was to stop spam
Discussion
But how does that work? Who controls this decision)
The relay the spammer is posting to.
The issue is that clients will need to adopt/be updated to handle PoW reqs from relays that implement it.
But, at the core, each relay is sovereign and dictates what it finds acceptable from actors. It can try to track spammers (by ip, npub, traffic patterns) or give up on that idea and just raise/lower difficulty of the PoW for all users at once.
The spammer can and will move to another relay.
Most likely, the spammer will be using their own relay.
You just want to be on the right ones. Maybe those that have PoW and each post shares the nonce.