The molecular docking of specific reverse transcriptase inhibitory ligands onto the molecular model of HIV-1 reverse transcriptase

Document Type : Original Article


1. Research Affairs, Behbahan Faculty of Medical Sciences, Behbahan, Iran. 2. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.



Background: HIV-1 reverse transcriptase (RT) is a crucial enzyme in HIV replication and AIDS progression. It consists of p66 and p51 subunits and converts viral RNA into double-stranded DNA for integration into the host cell's genome. Managing HIV/AIDS depends on inhibiting HIV-1 RT, achieved through nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Understanding RT's structure, catalysis, inhibition, and resistance has been vital for disease management.
Methods and Materials: To study the binding sites and interactions of reverse transcriptase inhibitors (RTIs) with HIV-1 RT, we utilized Molegro Virtual Docker for model preparation and docking. We also employed the SwissADME web tool for predicting physicochemical properties and pharmacokinetics of compounds of interest.
Results and Discussion: We investigated the binding site and affinity of antiretroviral drugs, including delavirdine, tenofovir alafenamide, and atavirdine, with the HIV-1 RT enzyme. Additionally, we evaluated factors such as gastrointestinal absorption, blood-brain barrier penetration, Pgp substrate status, and skin permeability to assess the efficacy of these drugs in treating HIV/AIDS. The findings of this study may help us understand the interactions and potential applications of these compounds with other drugs, ultimately improving antiretroviral therapy for managing HIV-1 infection.
Conclusion: Understanding the binding affinity, sites, and pharmacological properties of reverse transcriptase inhibitor compounds is crucial for developing effective antiretroviral therapies against HIV/AIDS.