Great to know that the issue has already been resolved and thanks for sharing the solution so that others experiencing the same thing can easily reference this! Since the Microsoft Q&A community has a policy that "The question author cannot accept their own answer. They can only accept answers by others", I'll repost your solution in case you'd like to "Accept" the answer : )
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Issue Symptom:
Getting an error while trying to test Out SMIME Extension in OWA (Outlook on the web)
-S/mime works fine in Outlook Desktop Client, Issue is only for OWA
-After Installation(enabling), It just keeps loading forever, Never stops or returns the error
Accessing the Extension page: edge://extensions -> Select Extension -> Select "errors" shows the below:
Error while receiving settings: [object Object]
"Unchecked runtime.lastError: Access to the specified native messaging host is forbidden."
Resolution:
-Seems to be working now in OWA in Edge after I used Set-SmimeConfig to enable the OWAIncludeSMIMECapabilitiesInMessage parameter.
-Also an important tip is that it does not work with unified labelling, Unless the Label's advanced settings have S-mime enabled.