Could you try the following procedure:
- Open Windows Defender Security Center.
- Click on Virus & threat protection.
- Click the Virus & threat protection settings option.
- Turn off the Controlled folder access toggle switch.
You could also try adding calibre's application collection to the allowed list in the Controlled Folder area but it was easier for me to move my calibre libraries into a new directory directly under my user directory (C:\Users\David\Calibre) and point calibre at the new locations.