I don't have experience with Electron apps but as long as the following conditions are met, it could work.
Is it possible to install an extension inside the embedded Chromium? Unfortunately, the necessary "Microsoft S/MIME" extension is not available in the official Chrome Web Store but at a custom repo (https://outlook.office.com/owa/SmimeCrxUpdate.ashx, see README.md), which may make the things a bit difficult.
Since it's just a proxy for the locally installed Native Messaging host, it may be possible to re-implemented it under a free license and bring it to the Chrome Web Store.
Do Electron apps look into the same directory for Native Messaging hosts as a regular Chrome (/etc/chromium/native-messaging-hosts/)? Can they use native messaging in general?
I would definitely be interested in implementing this together.
This looks super promising, thanks for sharing
Maybe it can be integrated into prospect mail?
https://github.com/julian-alarcon/prospect-mail/issues/321