PyPy 17x faster than Python. Can Python be sped up?

Question

Solving a recent Advent of Code problem, I found my default Python was ~40x slower than PyPy. I was able to get that down to about 17x with this code by limiting calls to

Answer 1

You can improve small things, but pypy will (most likely) always be faster in this task.

For both CPython and Cython:

• Don't read in the whole file at once. You can iterate on lines as you go, which saves you (re)allocation costs. This requires you to pre-allocate the array though.
• Maybe switch from a list to an array.

For Cython:

• Mark the variable types. Especially the counters as ints and the commands as an array of ints to skip most type checks.