I tune/play exclusively in Eb,as in,it's still A440[as far as easy understanding is concerned],but every string is 1 semitone flat,it makes using heavier gauge strings more tolerable,and it suits my little singing voice more.
Fortunately,most softsynths,always have a "semitone" option,so it[so far] has never been a problem,but I have wondered,about those that use 442,or more common 445.
For what it's worth,after toying with drop D,C sharp,C[or SOAD] C flat,I'll never go below Eb for the forseeable future,although,Eb,with the low Eb tuned down to Db is fun[Alice In Chains-"We Die Young"],but,after seeing how abysmal some of these ultra low tuned bands sound "Live",I ain't going down past the typical "one fret lower",that is loose enough for me

.