In Silico Drug Designing of HIV-1 Reverse Transcriptase Inhibitors

Abstract

The human immunodeficiency virus (HIV) is the causative agent of the acquired immune deficiency syndrom (AIDS). HIV attacks the human CD4+ T helper cell lymphocytes, which are a key component of the immune system. The antiretroviral therapy is a major HIV therapy, which bases on blocking the HIV replication by inhibiting the enzyme reverse transcriptase. HIV type-1 nucleoside and non-nucleoside reverse transcriptase (NNRTIs) are antiretroviral key drugs, which target protein domains of the reverse transcriptase. With the objective to design ligands for inhibiting a protein domain of the reverse transcriptase, we identified the active site of the reverse transcriptase and evaluated suitable ligands for this receptor site. Therefore, we applied in silico or computer-aided drug design – a very efficient tool in drug discovery. This enabled us to optimize dynamical and statical parameters and to perform homology modeling, model verification, binding site identification, and docking analysis to identify the ligand "lig_raj8_1" as the best inhibitor of the human reverse transcriptase. This ligand exhibits excellent drug likeness properties for in vitro clinical trials and is highly promising as a lead inhibitor of HIV1.