If [naturalism] is true, then all minds, and all the contents and powers and effects of minds, are entirely caused by natural [i.e. fundamentally nonmental] phenomena. But if naturalism is false, then some minds, or some of the contents or powers or effects of minds, are causally independent of nature. In other words, such things would then be partly or wholly caused by themselves, or exist or operate directly or fundamentally on their own.

— Richard Carrier

It's not a matter of whether they are "made of different stuff" but if they are made of stuff at all. A simulator is no more supernatural to us than we are to a boxed AI; we're both running inside the same material universe, just in different ways.