No, neither does restarting the server.
We had this problem in May, and then I solved it by deleting first one domain, that didn't fix it, then I deleted another domain - and re-applied the domain in question and voila it worked.
Today, I haven't got any domains to delete - but I can try to delete the domain in question and re-apply it again. However the domain is mentioned within mysql table settings_local_domains, and in the following two files:
C:\Program\Symantec\SMSSMTP\mta\delivery\etc\routing.txt
C:\Program\Symantec\SMSSMTP\mta\shared\locals.txt
So I suspect that either the MySql relationships are broken, or that another config file / queue pair doesn't exist - or some hash coded list perhaps - and that the cause could be some timeout occuring when we enter the domain through the control panel. It is though very troublesome for us. The server is very busy, often working at a 100% - conduit.exe and filter-hub.exe often fight for power.
/Peter