One thing that raises many scientists' suspicions about the nature of the universe, is just how well it all seems to work and, what's more, how easily we can put it all down in the form of equations.
We tend to take it for granted that the universe is governed by a set of immutable laws. We give these names like thermodynamics, gravity, magnetism and relativity, but these are just our ways of quantify the strict set of rules that reality appears to follow.
Another thing that is based on a strict set of rules that will always yield the same results if given the right input, is code. Computer code.
Could it be that the reason that physical laws are so computable (E = mc2, for example), is because that's the way it was programmed?
One rock-solid way of refuting the claim that the universe is a simulation, would be the discovery of uncomputable physics, something that we can't quantify with maths. Can you think of any?*
*Hint: No, you can't.