CoMFA 3D-QSAR Analysis of HIV-1 RT Nonnucleoside Inhibitors, TIBO Derivatives Based on Docking Conformation and Alignment

2004 ◽  
Vol 44 (6) ◽  
pp. 2167-2178 ◽  
Author(s):  
Zhigang Zhou ◽  
Jeffry D. Madura
Keyword(s):  
3D Qsar ◽  
Qsar Analysis ◽  
Nonnucleoside Inhibitors ◽  
Hiv 1

Computational Studies of 3D-QSAR on a Highly Active Series of Naturally Occurring Nonnucleoside Inhibitors of HIV-1 RT (NNRTI)

2020 ◽  
pp. 2050036
Author(s):  
Waqar Hussain ◽  
Arshia Majeed ◽  
Ammara Akhtar ◽  
Nouman Rasool
Keyword(s):  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Modeling ◽  
Qsar Analysis ◽  
Qsar Studies ◽  
Highly Active ◽  
Naturally Occurring ◽  
Zinc Database ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

HIV is one of the deadliest viruses in the history of mankind, it is the root cause of Acquired Immunodeficiency Syndrome (AIDS) around the world. Despite the fact that the antiviral therapy used against HIV-1 infection is effective, there is also rapidly growing cases of drug resistance in the infected patient along with different severe side effects. Therefore, it is of dire and immediate need to find novel inhibitors against HIV-1 Reverse Transcriptase (RT). In this study, the potential of naturally occurring compounds extracted from plants has been studied with the help of Three-Dimensional-Quantitative Structure–Activity Relationships (3D-QSAR) analysis. A total of 20 compounds, retrieved from a ZINC database, were analyzed with the help of 3D-QSAR to identify a potential inhibitor of HIV-1 RT. By evaluation of seven models generated with the help of MIF analysis and 3D-QSAR modeling, compound 3 (ZINC ID: ZINC20759448) was observed to outperform others by showing optimal results in QSAR studies. This compound has also been biologically validated by a recently reported previous study. Thus, this compound can be used as a potential drug against infection caused by HIV-1, specifically AIDS.

3D-QSAR Studies of S-DABO Derivatives as Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

2019 ◽  
Vol 16 (8) ◽  
pp. 868-881
Author(s):  
Yueping Wang ◽  
Jie Chang ◽  
Jiangyuan Wang ◽  
Peng Zhong ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Three Dimensional ◽  
Predictive Ability ◽  
3D Qsar ◽  
Binding Mode ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Reverse Transcriptase Inhibitors ◽  
Qsar Studies ◽  
Hiv 1

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The Docking/MMFF94s computational protocol based on the co-crystallized complex (PDB ID: 1RT2) was used to determine the most probable binding mode and to obtain reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set of 30 compounds on the basis of hybrid docking-based and ligand-based alignment. Results: The predictive ability of CoMFA and CoMSIA models was further validated using a test set of eight compounds with predictive r2 pred values of 0.843 and 0.723, respectively. Conclusion: The information obtained from the 3D contour maps can be used in designing new SDABO derivatives with improved HIV-1 inhibitory activity.

3D-QSAR, molecular docking and in silico ADMET studies of propiophenone derivatives with anti-HIV-1 protease activity

2021 ◽  
Author(s):  
Milan Jovanović ◽  
Nemanja Turković ◽  
Branka Ivković ◽  
Zorica Vujić ◽  
Katarina Nikolić ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Protease Activity ◽  
3D Qsar ◽  
In Silico Admet ◽  
Anti Hiv ◽  
Hiv 1

Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors

1995 ◽  
Vol 2 (5) ◽  
pp. 407-415 ◽  
Author(s):  
Jianping Ding ◽  
Kalyan Das ◽  
Henri Moereels ◽  
Luc Koymans ◽  
Koen Andries ◽  
...  
Keyword(s):  
Nonnucleoside Inhibitors ◽  
Hiv 1

scholarly journals Novel Nonnucleoside Inhibitors That Select Nucleoside Inhibitor Resistance Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase

2006 ◽  
Vol 50 (8) ◽  
pp. 2772-2781 ◽  
Author(s):  
Zhijun Zhang ◽  
Michelle Walker ◽  
Wen Xu ◽  
Jae Hoon Shim ◽  
Jean-Luc Girardet ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Nonnucleoside Inhibitors ◽  
Rt Inhibitors ◽  
Hiv 1 ◽  
M184v Mutation

ABSTRACT Mutations in and around the catalytic site of the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) are associated with resistance to nucleoside RT inhibitors (NRTIs), whereas changes in the hydrophobic pocket of the RT are attributed to nonnucleoside RT inhibitor (NNRTI) resistance. In this study, we report a novel series of nonnucleoside inhibitors of HIV-1, exemplified by VRX-329747 and VRX-413638, which inhibit both NNRTI- and NRTI-resistant HIV-1 isolates. Enzymatic studies indicated that these compounds are HIV-1 RT inhibitors. Surprisingly, however, following prolonged (6 months) tissue culture selection, this series of nonnucleoside inhibitors did not select NNRTI-resistant mutations in HIV-1 RT. Rather, four mutations (M41L, A62T/V, V118I, and M184V) known to cause resistance to NRTIs and two additional novel mutations (S68N and G112S) adjacent to the catalytic site of the enzyme were selected. Although the M184V mutation appears to be the initial mutation to establish resistance, this mutation alone confers only a two- to fourfold decrease in susceptibility to VRX-329747 and VRX-413638. At least two additional mutations must accumulate for significant resistance. Moreover, while VRX-329747-selected viruses are resistant to lamivudine and emtricitabine due to the M184V mutation, they remain susceptible to zidovudine, stavudine, dideoxyinosine, abacavir, tenofovir, and efavirenz. These results directly demonstrate that VRX-329747 and VRX-413638 are novel nonnucleoside inhibitors of HIV-1 RT with the potential to augment current therapies.

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