Manu Tuilagi will miss England's RBS 6 Nations opener against Scotland, coach Stuart Lancaster has announced.
Tuilagi has been ruled out of Saturday's Twickenham encounter with an ankle injury but could return for the second round of the championship against Ireland on Sunday week.
Lancaster also confirmed that prop Alex Corbisiero will be sidelined for the entire RBS 6 Nations with a knee problem.
"Manu has run out of time for Scotland and we'll make a call on him for Ireland early next week," Lancaster said.
Tuilagi was devastating during last autumn's record 38-21 victory over world champions New Zealand, scoring one try and creating two more.
The explosive 21-year-old is England's most dangerous player and, when fit, has been an ever-present in their midfield since making his debut in 2011.
"By the end of the week we expect Manu to be running fully and changing direction," Lancaster said.
"The message I'm receiving from the medical team is that he will be training fully by Tuesday or Wednesday next week, but I'll need to make a call earlier in the week. He won't be training properly until at least Friday.
"Manu is a big loss - he was outstanding against New Zealand. But he missed the first two games of last year's Six Nations because of a hamstring and it's an opportunity for someone else.
"It's disappointing for him, but it's not a long-term injury so he'll be back soon."
England must decide whether to draft in Billy Twelvetrees or Jonathan Joseph to partner Brad Barritt, while fly-halves Toby Flood and Owen Farrell are alternatives.
"We have a pretty good idea of how we'll rejig the midfield. We have our thoughts," Lancaster said.
"It changes the emphasis a little bit, but it won't fundamentally affect the way we play.
"Brad will be in the equation and we need to make sure we can still break the gainline and have physical defenders. We've got to have the ability to get across the gainline and defend."
The initial outlook on Corbisiero's knee problem was that he could return against France on February 23, but London Irish director of rugby Brian Smith revealed last night that his rehabilitation will take longer.
Lancaster, however, denies Smith's suggestion that the injury is more grave than has been made public.
"The reality is the surgeons recommended two weeks rest and said it would then take six to eight weeks to be back playing, so that will rule him out of the Six Nations," said Lancaster.
"Hopefully he'll be back around the final game against Wales, but the reality is he'll have to play two or three Premiership games first.
"It's a shame because everything I heard about the operation was positive, but it's going to take a while to get right. Everyone's positive and upbeat about his recovery.
"Alex is a big loss, but Joe Marler has played well for Harlequins recently. Mako Vunipola is improving all the time and Nick Wood was outstanding for the Saxons."
Gloucester fly-half Freddie Burns has been ruled out against Scotland and Ireland with knee ligament injury damage, while Wasps number eight Billy Vunipola is struggling with an ankle problem.