A knot that runs across the grain is the most dangerous, when it comes to chrysalling. Its basically like have an empty hole at that point.
I've never dealt with one that large, but I have plugged plenty of yew staves with "Dutchmans". Drill / ream the knot out and plug with a clean section of fresh wood. Use a bow makers epoxy, or something like urea formaldehyde/or resorcinol glue.
Easier said than done though. I would really need a closer look and dimensions to see how feasible it would be to try in your situation.