Dual inhibitor design for HIV-1 reverse transcriptase and integrase enzymes: a molecular 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 and integrase are two of three HIV-1 essential enzymes which perform important virus life cycle functions. In recent years, researchers started to design new inhibitors which could inhibit multiple targets for treatment of AIDS. In respect to this, RT and IN are two enzymes suitable for the development of dual inhibitors. To realize this aim, here we have designed new inhibitors by using approved reverse transcriptase and integrase inhibitors as drug design templates. Totally 426 ligands, which are filtered from 858 ligands by druggability properties were docked to crystal structure of reverse transcriptase and since there was no full-length structure of HIV-1 IN, same ligands were docked to Prototype Foamy Virus integrase structure. From the docking results, B099 was determined to be the best binding ligand to RT enzyme with a binding free energy of −12.63 kcal/mole and B249 was the best ligand for IN enzyme with a score of −19.83 kcal/mole. These binding scores demonstrate that these ligands are more active than Raltegravir for integrase and Rilpivirine for reverse transcriptase which are also used for docking method validation. B205, B214, B233, B242, B246, B249, B253 and B254 are the some of ligands found to have good binding scores for both enzymes and could be considered as new inhibitor candidates as dual inhibitors.

Communicated by Ramaswamy H. Sarma