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For the first time this season, the San Francisco 49ers will have to bounce back from a loss. They will see a familiar opponent in the Arizona Cardinals on Sunday, a team they beat 28-25 two weeks ago. The first game between the two was a close battle where the 49ers had to rely upon the arm of Jimmy Garoppolo for the first time in 2019 to win.

San Francisco’s last two games have been decided by three points, and with the looming uncertainty surrounding the kicking game (Robbie Gould’s quad remains injured), the 49ers need to play well to avoid any chance of an upset.

Justin Skule

Left tackle Joe Staley is most likely out on Sunday. After missing the previous six games, Staley injured his finger against Seattle on Monday. This means rookie Justin Skule will probably return to the starting lineup to protect Garoppolo’s blindside. Staley’s been the anchor of the offensive line for more than a decade, but he struggled against Seattle. The rust, mixed with Jadeveon Clowney and Jarran Reed’s stellar games, led to a lot of Garoppolo mistakes.

The 49ers will play a top-10 Arizona pass rush led by Chandler Jones and Terrell Suggs. Skule will have his hands full, but if he can keep Garoppolo upright, the quarterback should be able to avoid the mistakes that ultimately stung the 49ers in their first loss. Garoppolo’s poor showing was a surprise after having his best pro game the week before against Arizona.

In the week 11 Thursday Night Football matchup with Arizona, Garoppolo threw for 317 yards, four touchdowns and zero interceptions. That game of course had a healthy Emmanuel Sanders and a hobbled George Kittle, but it also had Skule at left tackle. Two weeks ago, the Cardinals’ defensive game plan was focused on stopping Tevin Coleman, forcing Garoppolo to beat them. Should Arizona approach the game in the same way on Sunday, expect Skule and the rest of the line to rise to the challenge.

Any Wide Receiver Not Named Deebo

Although the rookie had some drops on Monday, Deebo Samuel became a trustworthy receiver with his eight catches for 112 yards. Samuel’s success was a necessity as tight end George Kittle was out and Emmanuel Sanders exited early with a rib injury.

Outside of Samuel, San Francisco’s receivers made numerous mistakes, amplifying Garoppolo’s bad game with drops. If Sanders is unable to go on Sunday, someone from the group of Marquise Goodwin, Dante Pettis, Richie James and Kendrick Bourne will have to perform. That group of four all have their flaws and follies, but they also have shown flashes of productivity.

Goodwin has a role pretty much carved out in this offense. The vertical threat does not play the same position as Sanders, and his targets aren’t directly impacted by Sanders’ availability. If the safety falls asleep on his go-route, there isn’t a player in the league that can run him down. In terms of replacing Sanders in the slot, Bourne will most likely get the first crack at it. He is third on the team with 200 receiving yards and is tied for the lead with two receiving touchdowns. 

He most recently had 42 receiving yards and a touchdown against the Seahawks. Bourne’s problem is not getting open or making guys miss. It’s catching the ball. Against Seattle, Bourne had a couple costly drops, one of which fell in the hands of safety Quandre Diggs, and ultimately led to a touchdown. Just like Bourne, Pettis had costly drops against Seattle. It would be an understatement to say Pettis is in a sophomore slump.

 The high preseason expectations have vanished as he falls further down the depth chart. Yet, all could be forgiven with a strong showing against Arizona. Pettis caught a 21-yard touchdown in week nine against Arizona. If he can erase last week’s game from his mind, and build off his touchdown-performance, he could be a well-needed play-maker for the 49ers.

Raheem Mostert

As stated above, the Cardinals did their best to stop Coleman. Coleman struggled to get anything going, rushing for 23 yards on 12 attempts. San Francisco’s only ground success came via Matt Breida. The speed back has been a constant in the 49ers’ backfield, but was hobbled on Monday. As Breida’s injury left him ineffective against Seattle, reserve running back Raheem Mostert picked up 28 yards on six carries. 

Breida is unlikely to play this Sunday, which means Mostert will be the lead backup for Coleman. This is not an unfamiliar role for Mostert. The special teams ace has 61 carries for 335 yards this season, mostly while spelling Breida. Given the Cardinals’ success in shutting down Coleman the first time around, Mostert becomes a vital part of the rushing attack this week.

Dre Greenlaw

Fred Warner is a great linebacker, but he needs a partner for this defense to be whole. The biggest question heading into Monday’s matchup was “How will the 49ers replace Kwon Alexander?” Even if the 49ers could replace his talent, the on field emotional leadership he brought was thought to be completely lost.

Fifth round rookie linebacker Dre Greenlaw earned those lofty tasks, and performed quite well, intercepting MVP candidate Russell Wilson in overtime to prevent a game-winning drive. What was possibly more important for the long term success of this San Francisco defense was his motivation on the field. Safety Jaquiski Tartt told David Lombardi of The Athletic that Greenlaw energized his teammates in the huddle right before his interception. 

That ability to lead by example is a necessity for this 49ers defense. They do not have the luxury for Greenlaw to build this up over time. He will have some growing pains, but he needs to develop into a starting NFL linebacker on the fly. If he can replicate his performance on Monday with another confidence-building game on Sunday, the 49ers’ defense could be back to unbreakable.

DeForest Buckner

San Francisco’s depth along the defensive line will be tested Sunday as Ronald Blair III (ACL) was placed on IR and D.J. Jones (groin) is questionable. Blair and Jones were both underrated, key parts of this 49ers defense. The 49ers will rely upon a variety of reserves to replace their productivity. Yet, when looking for disruptors on the line, one should look no further than starting defensive tackle DeForest Buckner.

As teams are deservedly giving Nick Bosa added attention, Buckner’s importance has been on full display these last few weeks. The Cardinals neutralized Bosa in week nine, but Buckner was able to record a sack, two tackles for loss and a quarterback hit. He followed that performance up with five tackles, two fumble recoveries and a touchdown against Seattle. Just like Aldon Smith partnering with Justin Smith, Bosa and Buckner have paired to form a lethal 49ers pass rush. 

Teams essentially have to pick their poison with the two. You can double team Bosa or Buckner, but not both. As Bosa continues to receive the opposing offense’s focus, Buckner should see success from his defensive tackle position. Buckner and his comrades will be the first line of defense when it comes to stopping the mobile Kyler Murray and the variety of Arizona running backs. What hurt the 49ers’ defense most in their last matchup was the Arizona running game. 

Cardinals running back Kenyan Drake, who was thrust into starting duties with both David Johnson and Chase Edmonds out, gashed San Francisco for 110 rushing yards and a touchdown in week nine. Johnson has struggled to get healthy this season, and Edmonds has been limited in practice this week, meaning Drake could see the bulk of carries again on Sunday. 

Stopping a mobile quarterback will be nothing new for Buckner and the line. For the third straight week, the line will have to stop a deathly-quick quarterback. Like Wilson, Murray is lethal in the open field. Buckner can limit Murray’s creativity by blowing up the middle of the field with his bull rush ability. If he succeeds in doing so, the pressure will be on Bosa, Arik Armstead and the other pass rushers to hold the edge.