Garry Ringrose and Devin Toner have been ruled out of Ireland's Six Nations game this weekend in Scotland.
The Leinster pair picked up hamstring and ankle injuries, respectively, in the round one defeat to England at Aviva Stadium.
Up front, in the crucial engine room, Quinn Roux – who replaced Toner before the hour mark, is likely to start, with Iain Henderson and Tadhg Beirne still missing through injury.
In-form Munster second row Billy Holland has been called into the squad as cover, with Ultan Dillane the only other fit lock in the squad.
"Devin's out this weekend with his ankle, he's so tall, with his ankle, he's got to get his balance back and he'll be right,” said scrum coach Greg Feek.
“Hendy's [Henderson] still a wee way away, he's got a bit of a reputation for healing quite quickly but he's still a wee way away. Tadhg could be right in a couple of weeks, we just have to wait and see. We'll get an update next week.
“Quinn did really well at the weekend, he came on and put a couple of big hits in,” Feek added.
He's been leading the line-out in Connacht this year, he's really progressed there and matured as a player. He's been in our environment since the South Africa tour [summer 2016]. He's good in the scrum, mauling, as a tight forward he ticks a lot of the boxes. Luckily for us, we have good depth there at the moment.”
Keith Earls trained fully today, despite suffering a hip injury in the game against England, and he is likely to be fit to start in Edinburgh on Saturday.
But Ringrose will not be risked, with Robbie Henshaw available to move from full back to midfield – where he will revisit his Connacht partnership with Bundee Aki.
“Garry's hamstring isn't quite right so he won't be with us either,” said Feek. “We've got the fallow week after Scotland so it does give us a bit of a window.
“With the way the strength and conditioning department work, they're incredible in what they do and every year they get better.”
Ringrose and Toner will hope to play their part later in the championship, as will Beirne and Henderson, and there is still a hope that CJ Stander, who suffered a suspected fractured cheek bone and eye socket on Saturday, could return inside a month.
Stander's absence opens up the door to Seán O'Brien, Jack Conan or Jordi Murphy this weekend, while Rob Kearney could be another to benefit from the high injury count against England.
“Rob's good, he got through yesterday and today,” Feek said. “Rob gets on with it, when his body's feeling good, he's got good energy and experience. I'd say he's probably delivering coffees to Joe over the last few days as well.”