Fua and McClain were both third-round draft picks this year and have been starters since Week 1. Fua strained his right hamstring before Sunday's 38-19 victory against Tampa Bay and didn't play. McClain sprained his left knee during the first half and did not return.
It's unclear at this point if either player will need surgery.
The Panthers also signed former North Carolina State defensive tackle DeMario Pressley to the practice squad.
Nwagbuo played two seasons under Panthers coach Ron Rivera in San Diego. He has played in 31 games, including four this season for the Chargers, and started five.
Shirley was a fifth-round draft choice by Cincinnati in 2008 and spent one week with Seattle this year after being released by the Bengals.
The Panthers have lost 14 players to injured reserve -- seven on each side of the ball.
McClain was selected 65th overall and Fua lasted until No. 97.
McClain had 20 tackles, one sack, four quarterback pressures and one fumble recovery. Fua, whose primary job at the nose tackle is taking up space in the middle for others to make plays, had 15 tackles with one quarterback pressure.
Overall, Rivera has been extremely pleased with the play of both rookies, while acknowledging the Panthers have had to "take some punches like a little brother." Still, Rivera believes the experience they gained playing as rookies will be huge for the Panthers in coming years.
The Panthers host Atlanta (7-5) on Sunday.