Gentile Virginio was the son of Napoleone II and Francesca Orsini. On the death of his uncle Carlo, he obtained the reins of his prominent house, at the time an enemy to the King of Naples and an ally of the pontiff. Pope Sixtus IV appointed him general of his forces, which Virginio led to a victory over the Neapolitan army at the Battle of Campo Morto. Almighty due to pontifical benefices, Virginio took advantage of the disorder which followed Sixtus's death in order to exterminate the Roman house of Colonna, something he didn't manage completely due to the Sacred College’s restoring the order. During the reign of Innocent VIII, the Orsini family reached the peak of its power and held significant influence over the Roman Curia through Virginio's cousin, Cardinal Giambattista Orsini of Monterotondo. The ascension of Alexander VI to the papal throne changed the status quo in the Roman politics.
Afraid of the new Pope's intentions to curb the power of his audacious barons, Virginio approached King Ferdinand I of Naples, who was suspicious of Alexander's relations to King Ferdinand II of Aragon, his formal overlord. It was with Neapolitan financial help that Virginio bought the Roman castles of Cerveteri and Anguillara from Franceschetto Cybo, the son of Pope Innocent VIII. It seems that Alexander VI had already reached an agreement with Cybo over the two fortresses and their unexpected purchase by his chief vassal with Neapolitan money was considered by the Pope as an act of treason. Nevertheless, Alexander and Ferdinand were reconciled in the summer of 1493. When Charles VIII of France seized Rome in the December 1494, demanding from the Pope to crown him monarch of Naples, the Orsini family hosted his troops in its fortresses and clamored for Alexander VI's deposition together with the Colonna family and most of the Cardinals. Thus Virginio, who had also been named Constable of Naples, betrayed both the Pope and the Aragonese dynasty of Naples. Hoping to gain benefits for his house by the French king, Virginio followed the French on their campaign in Naples. After the defeat of the French in the Battle of Fornovo and the restoration of the Aragonese in Naples the same month, Virginio was arrested and imprisoned by Ferdinand II of Naples, the new Neapolitan king, with the consent of the Pope. He died probably of poison in the Castel dell'Ovo, in Naples, while Alexander VI was confiscating the Orsini strongholds in the Papal States in favor of the Borgia family.
