SANTA CLARA, Calif. -- Just as the San Francisco 49ers' offense seemed to be rounding into form over the past two weeks, that group has lost two more key contributors to injury.

Wide receiver Deebo Samuel and running back Jeff Wilson Jr., both of whom played major roles in Sunday's 33-6 win against the New England Patriots, are expected to miss extended time, according to coach Kyle Shanahan.

Samuel is dealing with a left hamstring strain and will "most likely" miss this week's game at the Seattle Seahawks and next week's home contest against the Green Bay Packers, according to Shanahan.

It's a big blow for an offense that had leaned heavily on Samuel since he returned from a Jones fracture in his foot in Week 4. Samuel had five catches for 65 yards against the Patriots before he departed.

"Deebo is a huge part of our offense, a huge part of our team," Shanahan said. "When you have a threat of someone who can hurt you whether it's blocking, whether it's catching, whether it's running, that always is an issue for defenses."

Wilson is the latest 49er to suffer a high left ankle sprain and is expected to go on injured reserve this week, which means he will have to miss at least the next three games. Quarterback Jimmy Garoppolo, linebacker Kwon Alexander and running back Raheem Mostert have dealt with or are currently dealing with high ankle sprains.

Wilson was in the midst of the best game of his career when his ankle got rolled up on at the end of his third touchdown run. He finished with 112 yards on 17 attempts and those three scores before departing.

"He was unbelievable," Shanahan said. "I was very happy for him and how hard he played. It was extremely unfortunate he got hurt. I know he's really disappointed in that because of how good he's been playing. But at least he'll be able to come back. It'll be a month, most likely, but he'll be back from it."

With Wilson set to join Mostert on injured reserve, the Niners are down to Jerick McKinnon and JaMycal Hasty as the only healthy backs on the roster. Tevin Coleman, who has been on injured reserve with a sprained knee, is eligible to return, though it remains to be seen if he'll be healthy enough to do so this week.

"I hope so," Shanahan said of Coleman. "I'm not sure yet, though. I'll be surprised if he gets out there fully for Wednesday, but I think that will be a late, end-of-the-week decision."

In addition to the injuries to Samuel and Wilson, wide receiver Richie James Jr. sustained a sprained ankle against the Patriots. James will be day-to-day this week.

The 49ers also made a pair of roster tweaks on Monday, releasing defensive back Parnell Motley and defensive lineman Alex Barrett. Those moves leave the team with 50 players on the active roster. One of the three open spots will go to edge rusher Jordan Willis when his trade from the New York Jets becomes official.

How the Niners fill those other two spots will depend on a combination of how the injuries to Samuel, Wilson and James play out as well as the status of players eligible to return from injured reserve, including cornerback K'Waun Williams (knee, hip) and Coleman.