The Molecular Docking of Specific Reverse Transcriptase Inhibitory Ligands onto the Molecular Model of HIV-1 Reverse Transcriptase

Document Type : Original Article

Author

1 Behbahan Faculty of Medical Sciences, Behbahan, Iran

2 Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

10.30476/tips.2024.102488.1239

Abstract

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. 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. 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. Understanding the binding affinity, sites, and pharmacological properties of reverse transcriptase inhibitor compounds is crucial for developing effective antiretroviral therapies against HIV/AIDS.

Highlights

Roohallah Yousefi (Google Scholar)

Keywords

References

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Trends in Pharmaceutical Sciences
Volume 10, Issue 2
June 2024
Pages 91-112

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