The computer would reboot in to a maintenance mode where it would boot in to a check mode. Hopefully off the network or some other source that couldn't be altered by a virus/malware.
The check mode would checksum all executable content and update its database, reporting all changed and added files. It could also check for known out of date executable files. All files would be checked against a A/V database too. If nothing fails the computer reboots back to the OS, else it is halted until repaired.
This still has two risks I can see, one is the BIOS is altered and subverted there. The other is non-executable content runs transient programs that do not survive reboot.