[At_Libitum]

I've developed the habit over the years of never running any installer from my system drive, so I am sure that this is not a requirement for Calibre's msi installer.

I'm not sure anymore where that setting is located, but there's a thing in windows that allows maintaining the ZONE:Identifier when you download stuff from the internet.

If it is activated and you've downloaded a file, then right-click and select Properties on the downloaded file, there is an Unblock button bottom right on the General tab. It may be the reason why the file refuses 'to be found' or rather why it fails to execute and produce that error