Ok, after reading through the source code of polib, I found this way to achieve, what I want:
entry = po.find('Email address')
if entry:
entry.msgstr = 'E-Mail-Adresse'
if 'fuzzy' in entry.flags:
entry.flags.remove('fuzzy')
This seems to be the way to go ...
In the case of pluralisation - just as an example:
entry = po.find('%s hour ago')
if entry and entry.msgid_plural:
entry.msgstr_plural['0'] = 'Vor %s Stunde'
entry.msgstr_plural['1'] = 'Vor %s Stunden'
The docs of polib should definitively be updated. Otherwise great tool.