Seals very emphatically do not affect entire fortresses of doom. 5SB has strict volume limits that mean no variant of the seal would ever affect something a large as a house even (in volume terms). It also cannot affect parts of an object, so support pillars are no good. This is something that only runes can do
Not affecting an entire fortress is why you use more than one of them. Volume limits are why you use them on thin, flat things (like a sheet stretched over the outside of each wall) if you're clever, though I don't know if Sasori is clever in that sense (and whatever defensive seals he has might have different constraints).
A runic explosion actually will destroy one, IIRC, and would regardless destroy the supporting seals, but I think a setup like I described might block most of the first explosion despite being destroyed by it.
Or he might have something else entirely. Seals don't go big, but they go esoteric sometimes, and can have very very high durability on effects that are immovable.
How specifically will they react that means RERs won't work? They can tunnel (but Iron Earth means it's difficult) they can set up barriers, (but RERs can likely demolish anything they can do). They can Reverse Summon (but then we can bury their exit point).
Most relevantly, scatter to multiple zones, so we can't hit them with RERs without re-aiming (which takes
a practice shot, which takes multiple turns, by which time they'd've moved again one or more standard actions per rune, which might give them a chance to move again) and can't hit both of them with the same barrage.
Doubt they have barriers that can
block an RER*, but if the barrier isn't in the same zone as the person it's protecting it'll block line of effect to their zone.
* well, maybe Kisame's jinchuuriki-scale techniques. Or susanoo, or the yata mirror (?), or some weird crow boss technique, but if Itachi is there we probably won't even get the first shot off and also he can come back to life with izanagi so basically I just to hope he's not present
Cast some S-rank buff jutsu (or very-long-ranged attack or something weird we didn't think of). This might not be enough to save them, but then again it might.
Is there an explosion release technique that makes you immune to explosions? Oro didn't mention one, so probably not.
If someone reverse-summons that won't help them win the fight but it does mean they'll survive and get the word out, a mixed result but heck, I'll take it.
I'm not saying we definitely wouldn't win if they survive the alpha strike, but I do think the chances go way down.
