England face an "uphill battle" against South Africa's pack in the absence of hooker Jamie George, says ex-British & Irish Lions prop Alex Corbisiero.
The injured George - called up when Luke Cowan-Dickie was ruled out - is likely to be replaced in the starting XV by Jamie Blamire, who has four caps.
Captain Owen Farrell is also injured and it is unclear if prop Joe Marler will play after isolating with Covid.
Corbisiero said George's absence was "potentially game-changing".
The Springboks' dominance up front was key to their 32-12 World Cup final win against England in 2019 - the last time the two sides met.
Speaking on BBC Radio 5 Live's Rugby Union Weekly, Corbisiero said the Springboks' wins against Wales and Scotland this autumn showed sides are "punished" when their "set piece isn't up to scratch" against the world champions.
As well as George's knee injury, prop Ellis Genge is isolating and Marler will finish his isolation on Thursday evening, meaning he will only be able to train once with England on Friday before Saturday's game at Twickenham.
"It's all hands on deck for England this week," said former England forward Corbisiero.
"What you're battling against South Africa is the best team at putting pressure on you at scrum time.
"Now we're going to have some inexperience out there. Blamire is a hell of a player, he's just limited in experience.
"For England now, it is an uphill battle at set piece with those guys missing."
Corbisiero added that Marler would be a "knight in shining armour" if he plays on Saturday, describing the prop as a "world-class operator".
"He has been tried and tested in big games like this and will be the mettle that England need," Corbisiero continued.
'It will be an ultimate Test match'
England forwards coach Matt Proudfoot agreed England were "missing a real quality operator" in George, but added that Newcastle's Blamire "is a fighter".
Proudfoot - who was South Africa's forwards coach for their most recent World Cup win - said fans at Twickenham could expect "an ultimate Test match".
The former Scotland prop said the World Cup final had not been discussed in England camp this week, with the British and Irish Lions' series defeat to the Springboks last summer a more useful preparation resource.
Proudfoot said: "The guys that were over there in the summer - there has been a lot of bringing understanding back into the squad. Those have been the conversations."
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