England rugby centre Manu Tuilagi will miss Sunday's Six Nations opener against Scotland at Twickenham with an ankle injury, coach Stuart Lancaster announced today.
Prop Alex Corbisiero has been ruled out of the entire championship with a knee problem.
Lancaster said England had "run out of time'' to sort out Samoa-born Tuilagi's ankle but he was confident the Leicester centre would be training fully next week.
Tuilagi's loss is a blow to England ahead of this weekend's clash as the powerful midfielder played a key role in their record-breaking 38-21 win over world champions New Zealand at Twickenham last time out in December, scoring one and helping create two of the team's three tries.
Lancaster needs to decide between the ball-playing Billy Twelvetrees and Jonathan Joseph as a midfielder partner for Brad Barritt.
"We have a pretty good idea of how we'll rejig the midfield. We have our thoughts,'' said Lancaster, due to name his team to play Scotland on Thursday.
"It changes the emphasis a little bit, but it won't fundamentally affect the way we play,'' he insisted ahead of the latest edition of rugby's oldest international fixture.
Corbisiero damaged his knee during England's tour of South Africa last year but returned to action only for the injury to cause problems again after he played in England's stunning victory over the All Blacks.
"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.
"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 (England's reserve team).''