O'Brien had won the three previous runnings of the Newmarket Classic before Andrew Balding's Kameko struck gold last year, when the race was run in June instead of its usual early-May slot in the calendar due to the COVID-19 lockdown.
St Mark's Basilica renews rivalry with stablemate Wembley, who was beaten a head into second in the Dewhurst on October 10 when the pair were last seen in public.
They could be joined in the line-up by fellow O'Brien contenders Battleground, who signed off his impressive juvenile campaign with a staying-on second in the Breeders' Cup Juvenile Turf at Keeneland, along with Van Gogh, another Group One scorer at two, plus Military Style, who beat Van Gogh by a neck before finishing down the field in the Group Two Vincent O'Brien National Stakes at the Curragh in mid-September.
Thunder Moon took top spot in the National and Joseph O'Brien's lightly-race colt is another to try and reverse form with St Mark's Basilica having been third in the Dewhurst, along with Devilwala (4th), Chindit (9th) and Jim Bolger's recent Leopardstown scorer Poetic Flare (10th).
Recent Newmarket conditions stakes winner Mutasaabeq has been supplemented as expected by trainer Charlie Hills and the Shadwell team, but most resistance to the Irish challenge could be put up by Godolphin and trainer Charlie Appleby, who has Master Of The Seas, Naval Crown and the highly-regarded Autumn Stakes winner One Ruler to call upon.
One Ruler was last seen in competitive action finishing second to Mac Swiney in the Vertem Futurity Trophy at Doncaster and Bolger has also left the latter in this weekend's Classic at the five-day stage.
One Ruler enjoyed an eyecatching racecourse gallop at the Craven meeting in Newmarket earlier this month and was subsequently supported to be one of the market leaders, but Appleby confirmed that William Buick would stay loyal to Master Of The Seas.
Speaking to godolphin.com, the trainer said: "Five days out from the Guineas, I couldn’t be happier with them. One Ruler has been progressing nicely at home, while Master Of The Seas has gone to the races and put the score on the board.
“It wasn’t an easy call for William, who rode Master Of The Seas in the Craven and then sat on One Ruler in a routine gallop at Moulton Paddocks last week.
“William asked some serious questions of Master Of The Seas in his race, and he was pleased with the response. I believed that’s what clinched it in the end. Of course, the final call comes at declaration time on Thursday."
There are 18 possible runners in the 2000 Guineas at this stage and the list is completed by Albadri, Legion Of Honour, Lucky Vega and the Balding-trained Mystery Smiles.
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