Virus scanners (pretty much all flavours) claim to use heuristic analysis of the binaries to detect likely threats. The main problem is that the bastards who write the malware can easily see if their code triggers some pattern and write some diversion to trick the heuristic pattern matching and then you get a game of cat and mouse.
I would trust email over USB too. The USB interface was designed in a more trusting time*, so if it claims it is an Ethernet card then many OSes will immediately start sending it traffic. If it had a built in 4G then it could easily MitM. Or it could emulate a keyboard and send the shortcut keys to do whatever the logged in user can do. They might even be able to do some interesting trick pretending to be a sound card and sending voice commands as if it was a microphone input. And that is without physical damage. There is a USB stick that you can buy that basically has a capacitor inside. It takes charge for a short time, then unloads all that energy on a few chips expecting 5V 1A maximum.
At least with email, they would have to embed a font in the PDF to pwn the machine.**
*It is fort Knox compared to FireWire though.
**And I wish that was a joke