Citation: Jian-Bo TONG, Xing ZHANG, Shuai BIAN, Ding LUO. Drug Design, Molecular Docking, and ADMET Prediction of CCR5 Inhibitors Based on QSAR Study[J]. Chinese Journal of Structural Chemistry, ;2022, 41(2): 220200. doi: 10.14102/j.cnki.0254-5861.2011-3268 shu

Drug Design, Molecular Docking, and ADMET Prediction of CCR5 Inhibitors Based on QSAR Study

Jian-Bo TONG ^{a, b,,} ,
Xing ZHANG ^{a, b} ,
Shuai BIAN ^{a, b} ,
Ding LUO ^{a, b}

a.
College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China
b.
Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi'an 710021, China

Corresponding author: Jian-Bo TONG, jianbotong@aliyun.com
Received Date: 27 May 2021
Accepted Date: 5 July 2021

Fund Project: Innovation Supporting Plan of Shaanxi Province—Innovation Research Team 2018TD-015the Natural Science Foundation of Shaanxi Province 2019JM-237

Figures(11)

The chemokine receptor CCR5 is a main and necessary co-receptor for which HIV can recognize and enter the cells, and has been identified as a potential new target for the design of new anti-HIV therapeutic drugs. Highly active CCR5 inhibitors can prevent HIV-1 from entering target cells and block the process of infection. In this study, HQSAR and Topomer CoMFA methods were used to establish QSAR models for 75 1-(3, 3-diphenylpropyl)-piperidinyl and urea derivatives, and cross-validation and non-cross-validation were performed on the generated models. Two models with good statistical parameters and reliable prediction capabilities are obtained: (Topomer CoMFA: q² = 0.687, r² = 0.868, r_pred² = 0.623; HQSAR: q² = 0.781, r² = 0.921, r_pred² = 0.636). Contour maps and color code maps provide a lot of useful information for determining structural requirements that affect activity. Topomer search technology was used for virtual screening and molecular design. Surfex-dock method and ADMET technology were used to conduct molecular docking, oral bioavailability and toxicity prediction of the designed drug molecules. Results showed that A/ASN425, A/GLY198 and A/TRP427 may be the potential active residues of CCR5 inhibitors evaluated in this study, with 40 newly designed 1-(3, 3-diphenylpropyl)-piperidinyl and urea derivatives which have the main ADMET properties and can be used as a reliable anti-HIV inhibitor. These results provide a certain theoretical basis for the experimental verification of new compounds in the future.
- HIV,
- CCR5 inhibitors,
- Topomer CoMFA,
- HQSAR,
- ADMET
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