Flanker Will Connors and wing Hugo Keenan will make their Test debuts when Ireland host Italy in Saturday's Six Nations clash in Dublin.
The uncapped Ed Byrne and scrum-half Jamison Gibson-Park are also in line for their Test debuts off the bench at the Aviva Stadium.
Bundee Aki and Garry Ringrose have fought off the intense competition at centre to forge Ireland's midfield duo, while Conor Murray has kept his place at nine.
Johnny Sexton is fit to captain head coach Andy Farrell's team from fly-half, with the 35-year-old having shaken off recent hamstring troubles.
Leinster back-rower Connors had been earmarked to feature against Italy in the build-up to the original match's March 7 schedule.
Four uncapped players in the squad for our #GuinnessSixNations return on Saturday.#ShoulderToShoulder #IREvITA https://t.co/k3V5NDbszl — Irish Rugby (@IrishRugby) October 21, 2020
The coronavirus pandemic-enforced delay to the tournament had put the 24-year-old's chances of a Test debut against the Azzurri in doubt, however.
But now Ireland boss Farrell has handed the in-form flanker his chance to impress, with the seasoned British and Irish Lions star Peter O'Mahony on the bench as cover.
Caelan Doris and the dependable CJ Stander complete the new-look back row.
Leinster wing Keenan also steps in for his Test bow, in a back-three shorn of Jordan Larmour, who faces up to 16 weeks on the sidelines after dislocating his shoulder.
James Lowe has been training with Ireland but the 28-year-old does not qualify on residency until November.
