Microsoft has recently published a Knowledge Base article that lists down recommendations to improve performance in Windows when running antivirus scanners.

Microsoft recommends that you not scan the following files and folders. These files are not at risk of infection. If you scan these files, serious performance problems may occur because of file locking.
Where a specific set of files is identified by name, exclude only those files instead of the whole folder. Sometimes, the whole folder must be excluded. Do not exclude any one of these based on the file name extension.
Microsoft Windows Update or Automatic Update related files:
1) The Windows Update or Automatic Update database file. This file is located in the following folder:
%windir%\SoftwareDistribution\Datastore
Exclude the Datastore.edb file.
2) The transaction log files. These files are located in the following folder:
%windir%\SoftwareDistribution\Datastore\Logs
Exclude the following files:
a) Edb*.log
b) Res1.log. The file is named Edbres00001.jrs for Windows Vista, Windows 7, Windows Server 2008, and Windows Server 2008 R2.
c) Res2.log. The file is named Edbres00002.jrs for Windows Vista, Windows 7, Windows Server 2008, and Windows Server 2008 R2.
d) Edb.chk
e) Tmp.edb
f) The following files in the %windir%\security path should be added to the exclusions list:
*.edb
*.sdb
*.log
*.chk
Note: If these files are not excluded, security databases are typically corrupted, and Group Policy cannot be applied when you scan the folder.
Group Policy related files:
1) Group Policy user registry information. These files are located in the following folder:
%allusersprofile%\
Exclude the following file:
NTUser.pol
2) Group Policy client settings file. These files are located in the following folder:
%Systemroot%\system32\GroupPolicy\
Exclude the following file:
registry.pol
To know about such files for Windows Server 2008 R2, Windows Server 2008, Windows Server 2003, Windows 2000, Windows XP too, visit KB822158.
However TrendMicro does not agree with it completely:
Following the recommendations does not pose a significant threat as of now but it has a very big potential of being one. Cybercriminals may strategically drop or download a malicious file into one of the folders that are recommended to be excluded from scanning or use a file name extension that is also in the excluded list.
We find it sensible for users to aim for better system performance. However, we also think that excluding certain file types or folders from anti virus scanning is not something novice users should tinker with. Doing so may expose the system to risks that can lead to an inconvenience far more severe than a slightly slower system.
In line with this, we advise users to educate themselves fully about these recommendations before taking any action. We recommend users not to exclude any file unless there is a critical reason to do so and be aware of the risks entailed by such an action.
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