Both　HIV-1　integrase　(IN)　and　the　central　catalytic　domain　of　IN　(IN-CCD)　catalyze　the　disintegration　reaction　in　vitro.　In　this　study,　IN　and　IN-CCD　proteins　were　expressed　and　purified,　and　a　high-throughput　format　enzyme-linked　immunosorbent　assay　(ELISA)　was　developed　for　the　disintegration　reaction.　IN　exhibited　a　marked　preference　for　Mn2+　over　Mg2+　as　the　divalent　cation　cofactor　in　disintegration.　Baicalein,　a　known　IN　inhibitor,　was　found　to　be　an　IN-CCD　inhibitor.　The　assay　is　sensitive　and　specific　for　the　study　of　disintegration　reaction　as　well　as　for　the　in　vitro　identification　of　antiviral　drugs　targeting　IN,　especially　targeting　IN-CCD.