Earlier quoted context omitted.
I'm actually interested in what other problems make Hy and similar languages infeasible. Even if a brief overview, as food for thought on the matter.
They aren't infeasible; a real lisp could target Python. However, just bolting on lisp syntax to python ends up in an uncanny valley of "not python" and also "not lisp." I would actually recommend watching the entire youtube video I posted earlier (Clojure for Lisp programmers). Rich talks about a lot of the design decisions that went into Clojure. Some decisions I agree with, some I don't, but there was thought into…
A good way to target a Lisp to Python might be to forget the Python AST and target its virtual machine directly.
The compiler could itself be written in its own target dialect, and bootstrapped with some existing Lisp.