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Registry changes only tend to be made when programs are installed/uninstalled/updated, so random changes can indicate the presence of the virus.
Some programs ship with attached spyware or adware and refuse to run when the undesired co-programs are removed; newer versions of Spybot replace the spyware binaries with inert dummies (designed to fool programs which require the spyware's presence).
In order to efficiently detect recently created programs, detection updates are released weekly along with other improvements such as added languages and better heuristics algorithms.
Spybot - Search & Destroy, abbreviated as Spybot S&D is a popular proprietary antivirus that works on Windows 95 and later.
Like most malware scanners, Spybot S&D scans the computer's hard disk and/or RAM for malicious software.