On Windows, this may be a corrupt index (MSF) folder. Go to run - %appdata%, find your Thunderbird email folder, and rename the suspect msf folder as [foldername].msf.bad
It is often the Trash folder, though sometimes the Inbox folder will go bad.
Restart t-bird and it will rebuild the index.
I keep all of my old email for many years, and this has saved me a number of times.
Have you tried excluding the Thunderbird profile folder from your anti virus scanning. Most lockups like you describe are caused by anti virus scanning, not corrupt files.
The fix I described was effective. Otherwise t-bird was dead.