(Photo credit: Gary A. Vasquez-USA TODAY Sports)

Week 3 of the NFL season kick offs with one of the two double-digit spread games on the slate, with the New York Giants (1-1) traveling to the San Francisco 49ers (2-0).

QUICK PICK

The cards are certainly stacked against the Giants, who are playing on a short week after a win against the host Arizona Cardinals last Sunday. They're also doing it without star running back Saquon Barkley, who suffered a sprained ankle in the win, which came only after the Giants snapped a six-quarter scoreless streak to begin the season.

Meanwhile, the 49ers have steamrolled their way to a 2-0 start, following a route at Pittsburgh with a hard-fought 30-23 win at the Los Angeles Rams. San Francisco finally gets its home opener, and it's in prime time as a 10.5-point favorite, with the 49ers' spread line backed by 81 percent of the total bets at BetRivers and 78 percent at BetMGM.

Prediction: 49ers 30-13

PROP PICK

Giants quarterback Daniel Jones has thrown at least one interception in three consecutive games. Extending that streak to four has been the fifth-most popular player prop at BetMGM, drawing 99 percent of the bets at -110.

Minus Barkley and likely forced to push the ball downfield while playing from behind, Jones is in an unenviable situation while facing a 49ers defense that already has five picks and 6.0 sacks on the young season.

KEY STAT

49ers quarterback Brock Purdy has thrown at least two touchdown passes in seven of his past eight regular-season games, while running back Christian McCaffrey has scored at least once in 11 consecutive games. McCaffrey making that 12 straight has been the most popular prop at BetRivers, where it has drawn 3.6 percent of the bets at -250.

THE NEWS

Jones is in the crosshairs without Barkley and the entire left side of the offensive line. Left tackle Andrew Thomas (hamstring) and left guard Ben Bredeson (concussion) are also out for Week 3.

"(Jones is a) huge challenge," 49ers coach Kyle Shanahan said. "It starts with his legs -- anytime you have that speed and you can run the ball like he does," Shanahan said. "They're willing to run him. He's willing to run. He's physical when he runs. He has the skill set to run away from people."

The 49ers know the next man up at running back rather well. Matt Breida gained 2,463 total yards with 10 touchdowns with the 49ers from 2017-19, then was traded to the Miami Dolphins.

"I just want to go out there and play for my team," Breida said. "At the end of the day, I'm grateful to still be playing in the NFL, you know I came undrafted, so just to be here I am blessed and whatever my team needs me to do, I'm going to do."

The 49ers have no injury concerns at running back.

McCaffrey, the NFL's rushing leader (268 yards) by 88 yards through two games, is set to take on a Giants defense being hit for 4.6 yards per carry and 136.5 rushing yards per game. Giants defensive coordinator Don "Wink" Martindale's inventive fronts, including a two-man line for multiple snaps against the Cardinals, aren't leading to much success or pressure on the quarterback to date.

The Giants are still looking for their first sack and takeaway this season. The 49ers allowed 15 pressures Week 1 at Pittsburgh, but brought that number down to just six in Week 2, according to Pro Football Focus.

But it hasn't helped that New York was outscored 46-0 in the first half by the Cowboys and Cardinals, all but erasing risk-taking from either offense. Dallas pitched a 40-0 shutout in Week 1.

While McCaffrey is a sure thing on Thursday night, the 49ers are planning to work Elijah Mitchell into the game plan. Shanahan said he wants to get McCaffrey more rest. He's on pace for nearly 1,000 snaps in the regular season.

Shanahan expects defensive end Nick Bosa to continue making an impact -- he had three pressures of Matthew Stafford in the 30-23 win over the Rams -- even if it isn't showing up on the stat sheet every week.

"He's getting back into football shape, getting back into his groove," Shanahan said. "He got better and stronger throughout the game, similar to last week in that aspect. He finished the game really strong and took a step forward from Pittsburgh."

The Giants have allowed 10 sacks in two games. While Bosa isn't yet on the board, second-year defensive end Drake Jackson leads the team with three sacks.

INJURY REPORT

The Giants will be without Barkley, Thomas and Bredeson on offense. Linebacker Azeez Ojulari (hamstring) also was ruled out on Wednesday.

49ers co-leader in receptions Brandon Aiyuk (shoulder) was among players dinged for San Francisco last week along with cornerback Ambry Thomas (knee). Aiyuk and Ambry Thomas were limited in practice on both Tuesday and Wednesday and were listed as questionable to face the Giants.

THEY SAID IT

"It's tough. Wink will always say he's our best defensive player because when he's on the field running the ball, we are on the sideline. Saquon is an incredible leader; this team is going to miss him, but we also have a 'next man up' mentality. Everybody has to in this league." --Giants linebacker Bobby Okereke on playing without Barkley.

--Field Level Media