Brock Purdy’s turf-toe injury sidelines the 49ers QB for up to five weeks, thrusting Mac Jones into Sunday’s matchup with New Orleans. Fantasy managers should scan the QB streamer list, with Daniel Jones, Trevor Lawrence, and even Aaron Rodgers cited as viable options in tougher spots.

Week 1’s injury avalanche continued with Austin Ekeler’s season-ending Achilles and George Kittle’s hamstring. Add in Xavier Worthy’s shoulder and Brock Bowers’s knee, and the waiver wire becomes a chessboard. Watch for sleepers like Harold Fannin Jr. and Emeka Egbuka to emerge for deeper leagues.

The Broncos head to Indianapolis aiming to stay undefeated, but Indy’s Week 1 explosion makes this a tougher test. Daniel Jones thrived for the Colts (272 yards, TD) as they scored on all seven possessions, while Denver’s defense pinned the edge with six different players recording a sack. Bo Nix must rebound after two picks and a fumble, while a sharper Broncos ground game from RJ Harvey and J.K. Dobbins adds balance. Alec Pierce’s big-play ability and Indy’s improving defense shape a fantasy-friendly showdown.

Fantasy focus centers on Pierce and Indy receivers, the Broncos’ backfield convergence, and how clean Nix’s decisions can be in a high-leverage road game. If Indy can sustain the same efficiency Jones showed in Week 1, they’ll push Denver in a tight, turnover-prone affair that could swing on a single big play or defensive stop.

Denver aims to flip a historical rough start by opening 2-0, leaning on a veteran defense and a run-heavy attack as Payton rebuilds the offense around Bo Nix. Indy arrives with a refreshed vibe and Daniel Jones orchestrating seven straight scoring drives in Week 1, setting up a clash of Denver’s defensive prowess against Indy’s high-functioning new-look unit.

For fantasy managers, Nix’s turnover risk vs. Indy’s secondary and Jones’ quick-strike rhythm against Denver’s defense are the key storyline drivers. Monitor how the Broncos protect the ball and control pace, while Indy tests Denver’s back-end and pressure at Lucas Oil. Week 2 fantasy pivots hinge on game-script and run/throw balance.

Five bold Week 2 predictions for Denver vs. Indianapolis shape a fantasy-friendly path: a 200+-yard rushing onslaught with one back eclipsing 100 yards; Bo Nix climbs to 70% completions with 200 passing yards, a touchdown and no interceptions, while the offense emphasizes the run early. Denver’s defense eyes a six-sack performance from different players, including a secondary contributor, plus three takeaways. Jeremy Crawshaw bumps to a 49.5-yard punt average on a handful of tries, while Payton’s plan leans into ball control and field-position leverage.

The Colts’ run defense is vulnerable, even as their pass defense shines; if Denver can sustain the ground game, the game plan should unlock better efficiency for Nix and keep the chains moving. The piece uses a Giants scenario to illustrate pressure-induced turnovers, underscoring how the Broncos’ defense and special teams could swing outcomes in a close contest. For fantasy bettors, focus on the running back workload, Nix’s efficiency, sack distribution, and Crawshaw’s punting windows.