Drug Properties and Drug Ligand-Binding Comparison Analysis on Tenofovir and Zidovudine as a Reverse Transcriptase Inhibitor of HIV-1

Keywords:

HIV-1, reverse transcriptase (RT), binding affinity, molecular docking, ADMET

Abstract

Objective: The human immunodeficiency virus (HIV) infection has been a public health concern with no available cure. It is recommended for HIV patients to be supplied with antiretroviral therapy (ART) as their lifelong treatment to help reduce the course of this disease. This paper utilized bioinformatics approaches to examine tenofovir and zidovudine as an inhibitor of reverse transcriptase (RT) enzyme in HIV-1.

Material and methods: The 3D Model of the RT enzyme was generated using Swiss-Model Expasy from the FASTA amino acid sequence obtained from Protein Data Bank (PDB). The enzyme then went through several modifications using PyMOL before inserting them into CASTp: Computed Atlas of Surface Topography of Proteins active site prediction software, as well as PyRx (Python Prescription Virtual Screening Tool) and BIOVIA Discovery Studio 2021 for molecular docking. PreADMET analysis was used to determine the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the two drugs.

Results: The results from molecular docking revealed that tenofovir possessed higher binding affinity towards HIV-1 RT rather than zidovudine. ADMET analysis showed that tenofovir have better Pgp-inhibitor absorption and blood brain barrier (BBB) distribution than zidovudine. Meanwhile, zidovudine possessed higher Fu with carcinogenic properties.

Conclusion: Both drugs exhibited poor at Caco-2 absorption with high passive MDCK permeability, tested positive for human intestinal absorption (HIA), have up to 30% bioavailability, proper plasma protein binding (PPB) and volume distribution (VD), may act as both CYP substrate and inhibitor, have moderate clearance (CL), long half-life (T_½), and possessed different toxicity and allergic properties.

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Drug Properties and Drug Ligand-Binding Comparison Analysis on Tenofovir and Zidovudine as a Reverse Transcriptase Inhibitor of HIV-1

Keywords:

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