Добрый день. А после перезагрузки надо по новой запускать виртуальное окружение или оно уже работает?
alex@alex-Latitude-D430:~$ sudo /home/alex/apyvirtproject/env/bin/pip install -U setuptools pip
WARNING: The directory '/home/alex/.cache/pip' or its parent directory is not owned or is not writable by the current user. The cache has been disabled. Check the permissions and owner of that directory. If executing pip with sudo, you may want sudo's -H flag.
Requirement already up-to-date: setuptools in ./apyvirtproject/env/lib/python3.6/site-packages (49.2.1)
Requirement already up-to-date: pip in ./apyvirtproject/env/lib/python3.6/site-packages (20.2.1)