(CNN) -- Manchester United received a major boost in their quest for an unprecedented quintuple as central defender Rio Ferdinand was passed fit to play in their Champions League last 16 return tie against Inter Milan on Wednesday.
England central defender Rio Ferdinand has been a key ingredient in United's recent success.
Ferdinand turned his ankle in the 4-0 thrashing of Fulham which put United into the semifinals of the FA Cup on Saturday and was rated a major doubt for the second leg with the two teams tied 0-0 after their San Siro clash a fortnight ago.
But the injury has responded well to treatment and manager Alex Ferguson told Press Association on Tuesday that both Ferdinand and another worry John O'Shea would take their places.
"They are both fit and they will both play," said the United manager. "They both trained for the first time this morning and that was important for us."
Ferdinand is expected to partner Nemanja Vidic in central defense with O'Shea coming in at right back.
The enticing match up sees the return to Old Trafford of former Chelsea boss Jose Mourinho, who is now at the Inter helm.
It is his first competitive outing in England since he left Stamford Bridge 18 months ago and the build-up has been dominated by talk that he could one day succeed Ferguson.
"In 20 years maybe," smiled Mourinho when asked if he might eventually become United manager. "I think Sir Alex might be here that long.
"He is tough, he is strong, he is happy, he loves it and he wins. Let him be here for another 20 years. I hope he is."
Mourinho feels there is an element of negativity about the Italian game which does not exist in England.
"Our Italian friends see football in a different way," said Mourinho. "In difficult moments, they see football as more of a drama.
"I have never been like that and that view improved further by working in England because there football is never a drama. In England football is always passion and pleasure.
"That is the feeling I want to give to my players tomorrow but for three weeks they have been speaking about the drama of Inter always going out in the last 16.
"I prefer to think in a different way. I prefer to think about the possibility of Inter knocking out the world champions. It is a different way at looking at the picture."
Mourinho also has worries in central defense with Marco Materazzi and Nicolas Burdisso picking up leg injuries in the 2-0 win at Genoa at the weekend which boosted Inter's hopes of retaining the Serie A title.
But defender Walter Samuel is fit to return and Brazlilian striker Adriano, on the bench against Genoa, should partner Zlatan Ibrahimovic as Inter look to grab a vital away goal.
United have selection posers up front with Carlos Tevez pushing for inclusion after scoring twice against Fulham to continue his rich vein of form.
Ferguson must decide whether to bring back Dimitar Berbatov, rested at the weekend, alongside Wayne Rooney with Cristiano Ronaldo playing his usual wide role.
"It is a very difficult decision for me to make, as I hate leaving great players out," Ferguson said.
United, who have already claimed the Club World Championship and the English League Cup, are topping the Premier League and looking to get past Inter in their defense of the Champions League.
They also face Everton in the semifinals of the FA Cup in their bid to complete a clean sweep of the major domestic and international club trophies.
Arch-rivals Arsenal also face Italian opposition in their return leg on Wednesday, visiting AS Roma with a 1-0 lead from the first leg.
Roma have several injury concerns ahead of the match in the Stadio Olimpico, but the Gunners have an improving injury list with teenage striker Theo Walcott set to get another outing.
He returned as a second-half substitute in Sunday's 3-0 FA Cup win over Burnley -- his first game since dislocating his shoulder nearly four months ago.
"Overall it feels fine. I still haven't experienced getting clattered yet so that's the next test," Walcott told the Press Association.
With Chelsea and Liverpool defending single goal leads from first leg ties against Juventus and Real Madrid respectively on Tuesday, all four Premier League clubs are favored to make the quarterfinals.
Spanish Primera leaders Barcelona are rated the major threat to English dominance and entertain French champions Lyon in the Nou Camp on Wednesday, having drawn the away tie 1-1 with Thierry Henry scoring a vital goal.
German champions Bayern Munich are the shortest-price favorites to reach the quarterfinals having beaten Sporting Lisbon 5-0 in the away tie a fortnight ago to bely their indifferent Bundesliga form this season.
Mourinho's former charges Porto, who famously upset Manchester United in the semifinals at Old Trafford five years ago, are also looking set to make the last eight having drawn 2-2 against Atletico Madrid in Spain.