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2:30 for first/A runs
If your final save is at the labs with roughly 25 minutes left. you can still salvage your run
use infinite knife
use any healing items as much as you want, including First Aid Sprays
save 0-3 times
and still get S+
It's under 2:30:00 for 1st scenarios, but under 2:00:00 for 2nd.
If you still have a save from the lab/sewers - load it and try to get to the end faster.
Without beeing the world biggest speedrunner you can unlock the underground passage in like 8-10 mins.
you cannot use infinite ammo weapons from previous playthroughs of S ranks, since the game will automatically lock the outcome to S. however, you can use an infinite knife (which actually helps a lot when you're fighting G stage 1) you can heal as much as you want (idk who thought healing was supposed to be limited in S+ runs) however, you can only use 3 ink ribbons for saves and you must complete the entire game in under 2:30 (A) 2:00 (B)
it's also very important to know the route on where to go and how to do the puzzles. time will drain no matter what you do unless you pause the game, or when a cutscene is playing. item box, inventory, map, or the typical puzzles midgame will not stop time. pick up stuff you need and are essential and don't nit pick items that are going to waste your time. personally, i didn't pick up the extra hip pouch in the safety deposit room, 10 inventory slots was enough for me through my S+ runs.
it's also important to know where to use your three saves too, since you have to save mostly at boss fights. your first save won't be used for quite awhile until you are about to fight G stage 2, your second save should be used on G stage 3, and the final save will be used right after you fight super tyrant (leon) or G stage 4 (claire).
not sure if i missed anything essential. i'm sure you know all of this by now, but i just wanted to point it out. good luck on your S+ runs if you attempt them!