McCoy was injured in the second quarter when he was tackled near the sideline on an eight-yard reception. Gillislee replaced McCoy as the lead running back, while Bush was used primarily as a receiver.
Gillislee has shown flashes of becoming a productive member of the Bills' running back rotation since joining the team last season. He possesses a nice burst to get to the second level and may end up receiving the most touches, though he probably won't become a true workhorse.
He'll carry extra value in leagues that provide bonuses for long touchdowns, as he's showcased big-play upside so far this season. That gives him the highest ceiling of the Bills backs—albeit still with some question marks, as he's yet to receive the normal workload of a workhorse back.
Bush's 2015 season came to an early conclusion due to a torn MCL suffered in a freak accident during a game against the then-St. Louis Rams. He hit the open market and remained a free agent until early August, when the Bills signed him to provide backfield depth.
Now, the 31-year-old veteran could become a useful fantasy commodity again in the short term, depending on the severity of McCoy's setback. The dual-threat back could step into a multifaceted role within the Buffalo offense, but he will most likely be used as a security blanket for quarterback Tyrod Taylor.
Bush stated after his signing that versatility is what led the Bills to sign him, per Chris Brown of the team's official website.
"It's something that we talked about here with the coaching staff, just all the different ways I can be used," he said. "That's kind of been what I've done throughout my career. That's something that Bills fans can definitely look forward to. They can understand I'm going to do my best and give everything I've got."
While Bush may not take over a solo feature role, he should be more involved in the offensive attack than he's been when McCoy has been healthy.
Jonathan Williams is also available, though he is still working to assert himself as a reliable option after Buffalo used a fifth-round pick on him in this year's draft. He has the tools to become a three-down contributor, but it's hard to know what his role will be right now. So he's just a speculative pickup from a fantasy perspective.
The Bills highlighted a touchdown run from him during the preseason:
Buffalo Bills @buffalobills
37 yards out? No problem. #BillsRunDeep https://t.co/sbLms104YF2016-8-27 02:30:48
Gillislee will be a must-add pickup for fantasy owners if he's still available. But regardless of how Buffalo decides to fill the void, its rushing attack will likely see a serious drop-off until McCoy is back to full strength.