I don't know if S3 Files implements fcntl() locking or does it correctly. But if it does, I believe SQLite should work on it correctly as well.
There have been many buggy NFS locking or caching implementations historically, which is why reason SQLite recommends against using it on NFS concurrently on multiple machines: https://sqlite.org/faq.html#:~:text=But%20use,time%2E
This SO reply suggests NFSv4 is better at this: https://unix.stackexchange.com/a/432519. But caveat it with this older reply: https://unix.stackexchange.com/a/1887
To the best of my knowledge (I worked a little on this long ago), on Linux even NFSv2 has done correct fcntl() locking for decades, if all the correct services are running and the options are set appropriately and it's Linux on both the client and server. But if something is not configured as it should be, then locking or caching may not work correctly.