@my1xt I just tested with Yubico key on the most recent Opera Stable version 53.0.2907.68 and I was able to login to Google mail with 2-steps verification where Yubico key was involved. No any issue met. What specific problem with U2F device have you met in Opera? Could you describe it please?

Hello!
If you disable "hardware acceleration" (under Browser section) in opera:config does it make the issue gone? (Ensure you have enabled "Advanced settings" in the bottom left side of opera:config in order to see "hardware acceleration" setting).

Indeed VPN service was off for some time tonight. Now it works again.