I'm pretty sure the future of anti-viruses will involve signature matching one way or another, because there's no way around that.
There are numerous ways around it. A whitelist is the simplest way. We have the technology to systematically verify the integrity of each piece of software on a computer (barring physical access) [1]. The current implementations of TPM have the potential for massive privacy violations and abuse, but I'm hopeful that projects like OpenCore will eventually lead to open source TPM designs. In any case, in such a system anti-virus is not even necessary.
More complex but less restrictive methods include:
(1) Building machine learning algorithms around a set of data that measures the normal operation of the machine. Because 99.9999999999% of the time Grandma's computer shouldn't be acting as a server.
(2) A feedback system built into your antivirsus where users report applications that don't work or have malicious behavior. Then Grandma can look up the greeting card creator she wants to install and see that 100 users have given the application 5/5 stars over a period of 6 months. Bonus points for open source applications where people will take the time to audit them for free.
There's tons of research in this area and I don't have time to reproduce a complete summery here. The point is that signature based detection is a method that is not sustainable in the long term because the number of unique malware variants is something that is growing exponentially. Most people don't even have anti-virus installed, and those that do have to deal with the fact that the AV slows the machine to a crawl.
Signature based AV is just a stopgap measure until we can properly implement our operating systems and detection methods. In the future we will have operating systems with trusted computing bases and detection methods based on behavior and crowd sourcing.