49ers are not going to be able to walk into Denver and line up and run the ball per the usual gameplan. They've heard about this Peyton Manning fella and realize that the only way to win will be to match blows, round for round.
The good news is that S.F. does have the weapons to put up some points, with a wide array of receiving options, as well as Kaepernick's ability to escape pressure and make plays with his feet.
The injuries continue mounting on the defensive side of the ball for the 49ers. In addition to Aldon Smith and Navarro Bowman's absence, they will now have to endure a gaping hole in the middle with Patrick Willis sidelined, as well as Chris Culliver in the secondary.
Peyton will find plenty of time in the pocket and be able to pick apart a secondary that cannot keep up with Denver's WR corps, especially down a starting corner. This will force the Niners to play with their foot on the gas, resulting in a game that goes Over the posted 48.