The two big keys are:
Manning releases the ball in about 2 seconds, which is the lowest in the league. This translates to 20 sacks, which is the lowest in the league. Thing is, to throw the ball in 2 seconds two things have to happen:
1. you HAVE to predetermine where you're going. Even manning can't make 3 legitimately good reads and get the ball out in 2 seconds. This isn't a Kaepernick predetermination, Manning finds the weak spot in a team's scheme and goes from there. We don't have a tell...we don't hide a weak spot...we line up and make you win matchups. Which means he's most likely going to hold the ball a bit longer, or he's going to throw some contested throws. Our DBs are going to have to get those balls. It's been proven in the playoffs that Manning will throw INT's. He averages something like 2.5 INTs in his playoff losses.
2. You have to have timing. Even elite WRs don't get consistent separation in 2 seconds. Manning is throwing the ball to a spot, and the WR is going to go get it. Now, this is why I think he stays away from Sherman. Sherm is cerebral: he knows what formations and what releases mean and where the WR is going based on that. He can run the routes for the WRs, which isn't giving Manning that open window to throw to. Another key is that Manning doesn't throw many back shoulder fades. He hits his guys in stride. I don't know if this is an arm strength thing or what, but he's so successful maybe he doesn't have to resort to that.
The other thing screwing up timing is that we chuck WRs at the line of scrimmage. We have 3 guys that can disrupt and hold up WRs right at the line. They can alter a WR's timing and route. Guys are going to get pushed off their release; they won't be at their spot, and they'll be there a step or so late. Hopefully this causes Manning to hold the ball or move to a different read. We need our rushers to get home. We don't even really need sacks, we just need Manning to move his feet and move in the pocket.
The other big key is that we are the best in the NFL at defending screen passes. D. Thomas took a screen pass 80 yards to the house. Moreno has been living off of screen passes and crosses in the middle. We are the best at closing and getting the ball carrier down close to the line of scrimmage.
Manning isn't very good at 3rd and longs. Something around 38% if I remember correctly. If we can stop the run and shut down those short passes, we're looking good. Manning doesn't want to hold the ball.