Manu Tuilagi is poised to make his first Six Nations start in six years after Ben Te'o was ruled out of Saturday's clash with Ireland by a side strain.
England must enter the title showdown in Dublin without their first-choice inside centre due to the injury sustained in training on Monday, paving the way for Tuilagi to be restored to the midfield and for Owen Farrell and George Ford to be reunited as twin playmakers.
In an additional blow, blindside flanker Brad Shields has failed to recover from his own side strain to ensure Mark Wilson will continue in the back row.
Seven players have been trimmed from Eddie Jones' training squad ahead of Thursday's team announcement, but Tuilagi is not among those heading home as he closes in on making a first Test start in any competition for four years.
The bulldozing 27-year-old Leicester centre has been stricken by serious knee, chest and groin injuries that have him cherishing every moment in the game – and superstitiously touching wood every time he says he is fit.
When asked if he is ready to start, Tuilagi replied: "Definitely. It helps a lot to come into the England environment.
"The way we train is next level in terms of the speed and intensity. That definitely helps you going into the international games.
"You appreciate it 100 per cent more after having so many injuries. Before, when you are always fit and playing, you don't really think about it because it hasn't happened to you.
"But when I have been out for a long time, now I have got the opportunity to play and I'm really thankful. I've got the opportunity again to do what I really love doing and I have to take it.
"Before, you just played. You didn't really think about it too much. I didn't have that much experience. You just wanted to get your hands on the ball. But when you get older and learn more about the game there is a lot more to it.
"There is a different way of getting over the gainline, which for me now is to go into a hole or gap. But sometimes there won't be a gap there so for me. So that bit is the same – run hard."
Te'o's absence points to a significant overhaul of the original plan, with Tuilagi's power present at outside centre and Ford and Farrell occupying 10 and 12.
Giant Bath wing Joe Cokanasiga has also yet to reach full fitness from a knee problem, excluding him from Eddie Jones' plans.
It is hoped that Te'o, Shields and Cokanasiga will recover for the round-two match against France and they are to stay at the squad's camp in the Algarve, where they will continue to receive treatment.
"They're not far away from where we want them to be, but obviously for a game of this magnitude we need everyone at 100 per cent," assistant coach Neal Hatley said.
Wilson, who is poised to deputise for Shields, was named England's player of the series last autumn, with three superb appearances at number eight and one at openside flanker propelling him into World Cup contention.
