Virustotal has no guarantee of finding if a file is infected, if the file contains a virus that has existed long enough to get onto the database of one of the 50 scanning engines used by virustotal then it will be detected, if it's a brand new virus then it will not be detected.
The best advice is NOT to run the file, but if someone ever found themselves actually NEEDING to run a file they couldn't be sure about then using a virtual machine is how they would do it. Also they would have system images for the main machine stored on external media, because in some cases viruses operating within a virtual machine can still do unpleasant things to the rest of the machine.
Also, just because something isn't malicious in a virtual machine doesn't mean it won't be malcious when it comes out, many viruses are coded not to act maliciously in a virtual machine so that they can avoid being analysed, but when they are run on a real machine they notice that fact and do their evil work. So if a file was run and found to be safe in a virtual machine it still couldn't be considered safe for use on a regular machine.
Edited by rp88, 18 August 2015 - 11:24 AM.
Back on this site, for a while anyway, been so busy the last year.
My systems:2 laptops, intel i3 processors, windows 8.1 installed on the hard-drive and linux mint 17.3 MATE installed to USB