[PeterT]

If you're truly desperate, one option would be to change the mutex used by calibre to prevent multiple instances running. One approach to this would be run standard calibre as is, and to run portable calibre from source, and override the mutex used by calibre portable.

See source file utils\lock.py and look at

if iswindows:
    def singleinstance(name):
        mutexname = 'mutexforsingleinstanceof'+__appname__+name
        mutex =  win32event.CreateMutex(None, False, mutexname)

__appname__ is calibre

singleinstance is called from gui2\main.py with the variable

singleinstance_name = 'calibre_GUI'

so maybe change that to

singleinstance_name = 'calibre_PORTABLE'

and always runs portable from source.

Remember though NEVER EVER EVER point both to the same library.

Also, this has NOT been tested and I am NOT RESPONSIBLE for any corruption that might happen.