From time to time in my guest machine (Xubuntu 22.00) mouse clicks stop working properly specially when I'm using the Intelij IDEA IDE. Sometimes also happen with the default Firefox Browser that comes with the system.
In order to solve the problem you can simply run the command bellow:
kill $(ps -aux | grep "VBoxClient --draganddrop" | awk '{print $2}')then the mouse clicks will immediatelly return to be consistent again. The command will kill all VBoxClient processess that were launched
with the argument --draganddrop (see the reference to know more details of the reason why this works).
You can also add a keyboard shortcurt to execute this command in your OS (given that, at least for me, this happen frequently).