Binding modes of two highly potent and nontoxic inhibitors of HIV-1 integrase

The complex structures of Human Immunodeficiency Virus Type 1 (HIV-1) integrase binding two highly potent and nontoxic inhibitors, lithospermic acid (M₅22) and lithospermic acid B (M₅32), were obtained using docking calculations. Docking results provided detailed information of their binding modes. The binding sites of M₅22 and M₅32 were similar to the inhibitor 5-CITEP. The lowest docking energies for HIV-1 integrase binding M₅22 and M₅32 are in agreement with their corresponding lower IC₅₀ values. Our results on the chemical structure difference between M₅22 and M₅32 show that the carboxyl and hydroxyl groups on the side-chain of M₅32 are important chemical groups which could help to increase the effect against HIV-1 IN replication.