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The birth and prosperity of this church was guaranteed during its early days by two important historical figures: the Doge Giustiniano Partecipazio and the eastern Emperor Leone V; upon the death of the former, the majority of the deceased's resources were left to the church by the his will. Even Leone V seems to have economically supported the construction of the building, it is also said that it was upon his request that the body of St Zechariah was sent to Venice, now buried inside the church that takes his name.
Proof of the relationship between this building and power was the annual visit on the second day of Easter: the Doge, accompanied by the Signoria, foreign ambassadors and the population in procession, went to visit the church; legend has it that the ducal horn - symbol par excellence of the dogal power - was donated by Pope Benedict III to Agostina Morosini, abbess of San Zaccaria, who in turn donated it to Doge Pietro Tradonico, who - by tragic coincidence- was murdered after leaving the church of San Zaccaria. This traditional annual event lasted until the fall of the Republic.
There were many restoration and reconstruction works done on the building in its long history. Some sources report that the restoration of the old building was carried out in the middle of the X century, however few elements are able to testify to this work. The crypt that still exists today can be attributed to the same period, built on the same model that had been adopted in San Marco, with two rows of small columns that divide the space into three aisles with a low rib vaulted ceiling.
A second period of work is attested to be between 1170 and 1174 and it seems that they then continued (the urns of the side altars of the main chapel bear the date "1176"), and they were probably due to the famous fire of 1106, during which the church of San Zaccaria suffered damages.
The presbytery was completely rebuilt in 1443 (two years later the wooden choir was added to the side walls, like in the church of Santi Giovanni e Paolo). At the same time new apses were built in the Gothic style while the old Romanesque elements of the church gradually disappeared. The three main chapels were renovated, of which the central one, dedicated to San Tarasios, surpassed the two lateral ones; observing the apsidal conch one can admire the frescoes by the Florentine artist Andrea del Castagno portraying the Saints Zechariah, John the Evangelist, John the Baptist (who was the son of the votive saint), Matthew and Mark all around the central figure of the Eternal Father.
Despite these works, the supporting walls of the church aroused concern due to their state of decay, prompting the nuns to insistently ask first the doge and later Pope Callixtus III to intervene and help preserve the church. Thus in 1456 they obtained an extraordinary grant to start both the restoration work on the old church and construction of the new church. Despite the custom of constructing a new building over an existing structure, it was decided to build the new church on the adjacent ground so that the longitudinally developed structures were parallel, but formed a single block through the overlapping of the left aisle of the old one with the right aisle of the new one.
Antonio Gambello was entrusted with the design of the new church and who later died in 1481; two years later Mauro Codussi was elected proto magistro: under his direction the framework originally conceived by Gambello was maintained, a design of three aisles divided into three cross vaults, the largest of which ends in an apse with a pentagonal base. Codussi inserted a double dome into the design (one internal hemisphere and another external wooden one which was double the height and cladded in lead) placed at the intersection of the two arms of the latin cross plan. Marble and black stone of Verona were used in the façade in order to obtain a chromatic scheme based on the contrast.
Many works are kept inside the church in addition to the decorations created by artists of the time, such as the left altar made in the XV century by Pietro Lombardo, or the statues and the tabernacle that were carved by Alessandro Vittoria (he sculpted almost all the sculptures inside the church). Among the paintings stands out the Sacra Conversazione by Giovanni Bellini painted in 1505, while in the chapel dedicated to St Athanasius (present in left aisle in the old church) is the Madonna with Child and Saints by Jacopo Palma il Vecchio. The The Birth of St John the Baptist by Jacopo Tintoretto is also kept inside the church.