C.J. Beathard takes over, as the 49ers are down to their third-string quarterback in a season highlighted by injuries. He's not much of a fantasy option during championship week while facing a much-improved Arizona defense (despite Chandler Jones being out for the season) that ranks #8 against the pass in DVOA and sports the seventh-best pressure rate (25.3%).
With Raheem Mostert out, Jeff Wilson Jr. takes over as San Francisco's lead back (with some Tevin Coleman and Jerick McKinnon mixed in). And the Niners offense could get a boost with George Kittle's return (the team's YPC typically improves when he plays too). Wilson Jr. is a hard runner who's always a threat at the goal line, and while his upside is capped some given Arizona's underrated defense and SF starting their third-string quarterback, Wilson should still be considered a top-20 fantasy back this week.
If Kittle is cleared to return, he's an immediate must start in fantasy leagues with the tight end position so thin. He's averaging the second-most receiving yards per game of his career and makes the entire offense (and your fantasy team) noticeably better when on the field.
Brandon Aiyuk will likely be shadowed by Patrick Peterson but should remain the focal point of San Francisco's offense (he's seen 29 targets over the last two weeks) with Deebo Samuel and Mostert out. Aiyuk is Pro Football Focus' #2 graded rookie this season, and he's one of the lone bright spots for San Francisco while looking like a future star. I have Aiyuk as a top-10 fantasy wide receiver and a must-start in fantasy leagues during championship week.
Kyler Murray has gotten 8.0 YPA with a whopping 24 touchdowns over seven home games this season, and he looked recovered from a shoulder injury last week. He's a top-three fantasy QB in Week 16, while Kenyan Drake is a bounce back candidate with Arizona as touchdown home favorites and Chase Edmonds' status uncertain while missing practice. DeAndre Hopkins versus Jason Verrett is an intriguing matchup, but the Cardinals offense should enjoy plenty of success with Javon Kinlaw, Richard Sherman and Jimmie Ward all dealing with injuries.