Dual inhibitor design for HIV-1 reverse transcriptase and integrase: A docking study

HIV-1, a member of Retroviruses’ Lentivirus family, is the causative agent of AIDS. The virus is common throughout the world and leaves the body vulnerable to infections by suppressing the human immune system. Reverse Transcriptase (RT) and Integrase (IN) are two HIV-1 enzymes which perform important virus life cycle functions. It has been started to design new drug design that inhibit multiple targets for treatment of AIDS in recent years. In respect to this, RT and IN are two enzymes suitable for the development of dual inhibitors. 426 ligands which are filtered by druggability properties from 858 ligands were docked to crystal structure of 4g1q.pdb and since there was no full-lenght structure of HIV-1 IN same ligands were docked to Prototype Foamy Virus (PFV) IN structure 3oya.pdb, which have same properties as HIV-1 IN catalyctic region by Autodock4 program. From the docking results B099 ligand was determined to be the best binding ligand to RT ezyme with a binding score of -12.63 kcal/mol and B249 was the best ligand to IN enzyme with a score of -19.83 kcal/mol. B051, B053, B099, B103, B107, B205, B206, B211, B213, B223, B231,B241, B242, B249, B250, B251, B253, B254, B308, B324, B352 and B353 were found to give good docking scores for both enzymes. As a result, the design of new ligands, which are dual inhibitor candidates, was realized.