Ireland remain the favourites to win the Six Nations Championship but their playmaker, Johnny Sexton, will be a conspicuous absentee from the opening game against Scotland. There had been a nagging doubt over Sexton’s recovery from a calf problem and the fly-half has been ruled out of the fixture at Murrayfield on Saturday.

The good news for Ireland is that Ulster’s Paddy Jackson is a fast-maturing replacement but the loss of the 63-cap Sexton is a significant blow to Joe Schmidt’s plans so close to the tournament. With the talented Joey Carbery of Leinster also sidelined by injury, Munster’s Ian Keatley has been summoned as potential bench cover.

One player does not necessarily determine the fate of his nation but the 31-year-old Sexton, when fully fit, has been a consistently influential figure for an Ireland side who won the Six Nations title in 2014 and 2015. Only four players in history have scored more Six Nations points and his midfield understanding with Leinster team-mates Robbie Henshaw and Garry Ringrose is among Ireland’s key weapons.

Also missing with a hamstring problem is the Munster flanker Peter O’Mahony, with the wing Andrew Trimble also highly doubtful with a tight groin. Sexton picked up his calf problem against Castres in the final round of the European Champions Cup pool matches and it remains unclear if the fly-half will be ready for Ireland’s trip to Italy next week. “It’s better to leave him out this weekend,” Ireland’s forwards coach, Simon Easterby, said. “We don’t want to compromise his calf any further.”

The British & Irish Lions management will be among those monitoring his recovery closely, with the tour to New Zealand fast approaching this summer. The Lions coach, Warren Gatland, seems certain to be without the Scotland prop WP Nel, who has had to undergo surgery to repair a damaged disc in his neck following a collision during Edinburgh’s Challenge Cup game against Harlequins.

England and Wales also have injury concerns on the eve of the tournament. The forwards Taulupe Faletau (knee) and Luke Charteris (fractured hand) are out of Wales’s game against Italy in Rome while England’s George Kruis’s participation is once again up in the air after he injured a knee in training in Bagshot.

The Saracens lock, just back from a fractured cheekbone, will be assessed on Wednesday and Eddie Jones may yet be required to start Joe Launchbury and Courtney Lawes in the second row.

Leicester’s Ellis Genge has also been retained as loosehead prop cover in case Joe Marler suffers any late setbacks between now and the Test against France on Saturday, with Northampton’s Teimana Harrison also included in a 25-man squad. James Haskell did not take part in all aspects of training but is expected to be fit enough to feature as a replacement. Maro Itoje is in line to start at No6.

England have also experienced some late disruption on the wings. An accidental clash of heads in training left Jonny May requiring stitches while Jack Nowell had to miss the session for personal reasons. The Exeter wing is due to rejoin the squad on Wednesday evening.

The full-back Mike Brown insists Jones’s squad will not be fixating on the possibility of a 15th successive Test win – a feat not achieved by any previous England side – or chasing back-to-back grand slams. “It’s been the same since Eddie took over,” Brown said. “It’s next‑game focus and that’s France. The only thing that could come in is complacency but I don’t think with this group of players that it will.

“If one person was to get complacent that would be stamped out very quickly. We’re very much on that. We know what it looks like, we know what can happen if it comes in to one person – it will breed.

“That will not be accepted in this group so I don’t think there’s any danger of that. We are confident because we believe in each other’s ability, we believe in the work we’re doing and we know how hard we’re preparing every time we meet up.”

Brown has also revealed there is fierce competition within the squad to outdo each other in the new vision awareness exercises being conducted by Dr Sherylle Calder. The early clubhouse leader is Saracens’ Alex Lozowski, with Worcester’s Ben Te’o bringing up the rear. “There’s a leaderboard each week,” Brown said. “I just enjoy seeing Te’o at the foot of it. He hates it. He doesn’t like getting hammered by anyone. It’s always good fun when he’s at the bottom.”

England squad v France, Twickenham, Saturday

Forwards Cole (Leicester), Genge (Leicester), George (Saracens), Harrison (Northampton), Hartley (Northampton), Haskell (Wasps), Hughes (Wasps), Itoje (Saracens), Kruis (Saracens), Launchbury (Wasps), Lawes (Northampton), Marler (Harlequins), Mullan (Wasps), Sinckler (Harlequins), Wood (Northampton)

Backs Brown (Harlequins), Care (Harlequins), Daly (Wasps), Farrell (Saracens), Ford (Bath), Joseph (Bath), May (Gloucester), Nowell (Exeter Chiefs), Te’o (Worcester), B Youngs (Leicester).