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Henrikh Mkhitaryan scored a brilliant solo goal on the hour-mark to cancel out Jose Callejon's opener just minutes earlier - only for Lorenzo Insigne to decide the game in the final 10 minutes with a fine curling strike.
Coach Paulo Fonseca changed 10 players and the system for the match following Thursday's home defeat against Udinese, although he was forced to switch his three-man defence 30 minutes into the contest after Chris Smalling picked up an injury.
Pau Lopez, making his first start after returning from injury, was active throughout - making a number of fine saves to deny the likes of Arek Milik, Callejon, Fabian Ruiz and Mario Rui.
The Giallorossi had their chances too - Lorenzo Pellegrini going close twice in the first half - but had no answer to Insigne's late effort.
Fonseca's side are back in action on Wednesday, as they host Parma at the Stadio Olimpico.
Imperium Partners
Centurion Partners
