Any chance you ran "apt-get autoremove" or disk janitor recently? I had
some odd problems with a few python-based applications a while back after
allowing ubuntu to autoremove some things that it said were unnecessary. One
of the things removed was python-related. I don't remember what. I had no
idea what I was doing at that point.

Just curious, but have you verified the ebook files are not corrupt? What
version of Calibre are you using? Also, have you manually checked you have
all the dependencies and their proper version numbers (including python?).

check the bottom of this page for a dependency list:
http://calibre-ebook.com/download_linux