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Manu Tuilagi ruled out of Six Nations opener against Scotland and may miss Ireland trip

Stuart Lancaster forced to rejig midfield while injury forces Alex Corbisiero to sit out the entire tournament

If the uniquely fearsome Manu Tuilagi, not so much the X-factor player in England's back division as the XXX-factor one, was within a few minutes of playing Heineken Cup rugby for Leicester nine days ago, he is now the best part of a fortnight away from representing his adopted country in the Six Nations Championship. As a result, the red-rose coach, Stuart Lancaster, has no choice but to field a new midfield combination against Scotland at Twickenham this weekend – much to the unbridled joy of the men from north of the border.

Tuilagi is suffering from a sprained ankle: not a common or garden sprained ankle, but an unusually complicated version that has proved resistant to the usual treatment and frustrated the England medical staff charged with getting the Samoa-born centre fit for Calcutta Cup duty. Worse still, he may also miss the second match of the series in Ireland, who have a half-decent No 13 of their own in Brian O'Driscoll.

"Manu has run out of time for the Scotland game," Lancaster announced yesterday. "Everything I'm hearing from the medics suggests he will be running flat out by this Friday or Saturday and I have every confidence he will train with us next week. But it remains to be seen. Fortunately, we have an eight-day turnaround between Scotland and Ireland, so we'll be able to make a call early in the build-up to Dublin.

"It's a big loss. He was outstanding for us in the autumn, against the All Blacks in particular, and it's a blow to lose him. But this is the kind of injury that could go again if it's not dealt with properly, so we don't want to rush him. The important thing to understand is that it's not a long-term issue. Also, we were without him this time last year and won in both Edinburgh and Rome."

Lancaster also confirmed that Alex Corbisiero, his influential loose-head prop, was out of the entire tournament following surgery on a chronic knee problem that will, even if he makes the best possible recovery, require careful managing for the rest of his career. "This latest operation was successful and the news is positive, but it's going to take Alex a while to get back," the coach said, no doubt with a heavy heart.

While Lancaster had reconciled himself some time ago to losing Corbisiero, at least for the early part of the Six Nations, the sudden loss of Tuilagi, the human bowling ball, is another matter entirely. While neither of the other loose-head specialists in the squad, Joe Marler of Harlequins and Mako Vunipola of Saracens, are blessed with Corbisiero's highly developed footballing intelligence, they are more than capable of performing the fundamentals of the No 1 role to international standard. Tuilagi, on the other hand, is as different as different gets.

"I'm not sure there is a like-for-like replacement for Manu," remarked Lancaster when asked if he would simply replace his injured outside centre with a fit one, in the shape of the London Irish midfielder Jonathan Joseph.

His refusal to respond with a simple "yes" may simply have been a ruse to keep the Scots guessing, but it might equally have indicated a gnawing suspicion that Joseph has yet to revisit the heights he reached in South Africa last summer.

The coach has options beyond hanging Tuilagi's outsized shirt on Joseph's more slender frame. He could, for instance, restore his most experienced player, Toby Flood, to the outside-half berth and run the two Saracens midfielders, Owen Farrell and Brad Barritt, at centre – the role they performed together at the start of last year's Six Nations. Yet Farrell's game-management contribution at No 10 against the New Zealanders in December was so valuable, it is difficult to imagine Lancaster being in any rush to reposition him now.

Billy Twelvetrees, on the other hand, offers answers to a number of difficult questions. The uncapped Gloucester centre has size on his side – at 6ft 3in and the best part of 16st, he should be able to cope with anything the Scots offer in the tale-of-the-tape department – and has a big kicking game from both hand and tee. He also has one of the best running passes in the land. Indeed, it would be no surprise to see him nail down the No 12 position well ahead of the home World Cup in 2015.

"All options are open," said Lancaster, who was at his most cryptic in discussing the weekend's midfield possibilities. "Scotland are not a small side and we'll need to match them physically, but we won't be picking our side on the basis of who they pick in theirs. We'll select the team we think gives us the best chance of winning and we have three more important training sessions ahead of us before the decision has to be made."