User blog comment:Jopjopjop/Volume 20 Spoilers/@comment-201.79.38.59-20150808012315/@comment-26285797-20150808125457

Shiva said that only Ophis in her prime and Great Red at their full powers together could destroy 666. Even simply destroying 666 is impossible. At this point, Rossweise is the trump card, but only if she succeeds in her research to seal 666 away. Yes, Issei has powers from Great Red and Ophis, but he'd have to be able to use their full powers together to defeat 666, I don't see that happening.