Calibre 4.0 Can't open database error

I am running Calibre on my ASUS ROG running Windows 10. The library is on the F: drive.

Three days ago I upgraded Calibre to 4.0 and everything was working fine. Yesterday there was a windows update and all drives except the C: drive gave and I/O error. I fixed the issue with the I/O errors, but now Calibre is not working.

raceback (most recent call last):
File "site-packages\calibre\gui2\main.py", line 304, in initialize_db
File "site-packages\calibre\db\legacy.py", line 82, in __init__
File "site-packages\calibre\db\legacy.py", line 47, in create_backend
File "site-packages\calibre\db\backend.py", line 401, in __init__
File "site-packages\calibre\db\backend.py", line 1150, in user_version
File "site-packages\calibre\db\backend.py", line 865, in conn
File "site-packages\calibre\db\backend.py", line 291, in __init__
CantOpenError: CantOpenError: unable to open database file

I checked the forums and added the Calibre folder to the exceptions for both Avast Antivirus and Windows Defender. This did not solve the problem. I then downloaded Calibre 4.1 and installed that and still getting the same error.

I uninstalled 4.1 and re-installed 4.0 and it is still not working. My entire setup is local to my laptop.

Can anyone suggest other steps to troubleshoot this issue?

Best Regards,

Kashyap