HIV-1 Integrase Inhibitor Interactions at the Active Site:  Prediction of Binding Modes Unaffected by Crystal Packing

2000 ◽  
Vol 122 (25) ◽  
pp. 6136-6137 ◽  
Author(s):  
Christoph A. Sotriffer ◽  
Haihong Ni ◽  
J. Andrew McCammon
Keyword(s):  
Active Site ◽  
Crystal Packing ◽  
Integrase Inhibitor ◽  
Binding Modes ◽  
Site Prediction ◽  
Hiv 1

Active site binding modes of curcumin in HIV-1 protease and integrase

2005 ◽  
Vol 15 (14) ◽  
pp. 3364-3368 ◽  
Author(s):  
Opa Vajragupta ◽  
Preecha Boonchoong ◽  
Garrett M. Morris ◽  
Arthur J. Olson
Keyword(s):  
Active Site ◽  
Binding Modes ◽  
Hiv 1 ◽  
Site Binding

Correlation of Biological Activity with Active Site Binding Modes of Geminal Disulfone HIV-1 Integrase Inhibitors

ChemMedChem ◽  
2006 ◽  
Vol 1 (9) ◽  
pp. 959-964 ◽  
Author(s):  
D. Christopher Meadows ◽  
Dean J. Tantillo ◽  
Jacquelyn Gervay-Hague
Keyword(s):  
Biological Activity ◽  
Active Site ◽  
Binding Modes ◽  
Integrase Inhibitors ◽  
Hiv 1 ◽  
Site Binding

Active Site Binding Modes of HIV-1 Integrase Inhibitors

2000 ◽  
Vol 43 (22) ◽  
pp. 4109-4117 ◽  
Author(s):  
Christoph A. Sotriffer ◽  
Ni ◽  
J. Andrew McCammon
Keyword(s):  
Active Site ◽  
Binding Modes ◽  
Integrase Inhibitors ◽  
Hiv 1 ◽  
Site Binding

Active site binding modes of dimeric phloroglucinols for HIV-1 reverse transcriptase, protease and integrase

2010 ◽  
Vol 20 (15) ◽  
pp. 4427-4431 ◽  
Author(s):  
Pawan Gupta ◽  
Rajender Kumar ◽  
Prabha Garg ◽  
Inder Pal Singh
Keyword(s):  
Reverse Transcriptase ◽  
Active Site ◽  
Binding Modes ◽  
Hiv 1 ◽  
Site Binding

Application of Molecular Docking for the Development of Improved HIV-1 Reverse Transcriptase Inhibitors

2020 ◽  
Vol 16 ◽  
Author(s):  
Arash Soltani ◽  
Seyed Isaac Hashemy ◽  
Farnaz Zahedi Avval ◽  
Houshang Rafatpanah ◽  
Seyed Abdolrahim Rezaee ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Binding Capacity ◽  
Binding Pocket ◽  
Ligand Docking ◽  
Binding Modes ◽  
Wild Type ◽  
Parent Molecule ◽  
Discovery Studio ◽  
Approved Drugs ◽  
Hiv 1

Introoduction: Inhibition of the reverse transcriptase (RT) enzyme of human immunodeficiency virus (HIV) by low molecular weight inhibitors is still an active area of research. Here, protein-ligand interactions and possible binding modes of novel compounds with the HIV-1 RT binding pocket (the wild-type as well as Y181C and K103N mutants) were obtained and discussed. Methods: A molecular fragment-based approach using FDA-approved drugs were followed to design novel chemical derivatives using delavirdine, efavirenz, etravirine and rilpivirine as the scaffolds. The drug-likeliness of the derivatives was evaluated using Swiss-ADME. Then the parent molecule and derivatives were docked into the binding pocket of related crystal structures (PDB ID: 4G1Q, 1IKW, 1KLM and 3MEC). Genetic Optimization for Ligand Docking (GOLD) Suite 5.2.2 software was used for docking and the results analyzed in the Discovery Studio Visualizer 4. A derivative was chosen for further analysis, if it passed drug-likeliness and the docked energy was more favorable than that of its parent molecule. Out of the fifty-seven derivatives, forty-eight failed in druglikeness screening by Swiss-ADME or in docking stage. Results: The final results showed that the selected compounds had higher predicted binding affinities than their parent scaffolds in both wild-type and the mutants. Binding energy improvement was higher for the structures designed based on second-generation NNRTIs (etravirine and rilpivirine) than the first-generation NNRTIs (delavirdine and efavirenz). For example, while the docked energy for rilpivirine was -51 KJ/mol, it was improved for its derivatives RPV01 and RPV15 up to -58.3 and -54.5 KJ/mol, respectively. Conclusion: In this study, we have identified and proposed some novel molecules with improved binding capacity for HIV RT using fragment-based approach.

scholarly journals No difference in HIV-1 integrase inhibitor resistance between CSF and blood compartments

2021 ◽  
Author(s):  
Basma Abdi ◽  
Mouna Chebbi ◽  
Marc Wirden ◽  
Elisa Teyssou ◽  
Sophie Sayon ◽  
...  
Keyword(s):  
Integrase Inhibitor ◽  
Routine Care ◽  
Biological Data ◽  
Recombinant Form ◽  
Hiv Integrase ◽  
Resistance Mutations ◽  
Clinical Routine ◽  
Inhibitor Resistance ◽  
Hiv 1

Abstract Background Little is known about HIV-1 integrase inhibitor resistance in the CNS. Objectives This study aimed to evaluate integrase inhibitor resistance in CSF, as a marker of the CNS, and compare it with the resistance in plasma. Methods HIV integrase was sequenced both in plasma and CSF for 59 HIV-1 patients. The clinical and biological data were collected from clinical routine care. Results Among the 59 HIV-1 patients, 32 (54.2%) were under antiretroviral (ARV) treatment. The median (IQR) HIV-1 RNA in the plasma of viraemic patients was 5.32 (3.85–5.80) and 3.59 (2.16–4.50) log10 copies/mL versus 4.79 (3.56–5.25) and 3.80 (2.68–4.33) log10 copies/mL in the CSF of ARV-naive and ARV-treated patients, respectively. The patients were mainly infected with non-B subtypes (72.2%) with the most prevalent recombinant form being CRF02_AG (42.4%). The HIV-1 integrase sequences from CSF presented resistance mutations for 9/27 (33.3%) and 8/32 (25.0%) for ARV-naive (L74I, n = 3; L74I/M, n = 1; T97A, n = 1; E157Q, n = 4) and ARV-treated (L74I, n = 6; L74M, n = 1; T97A, n = 1; N155H, n = 1) patients, respectively. Integrase inhibitor resistance mutations in CSF were similar to those in plasma, except for 1/59 patients. Conclusions This work shows similar integrase inhibitor resistance profiles in the CNS and plasma in a population of HIV-1 viraemic patients.

scholarly journals Activity of linked HIV-1 proteinase dimers containing mutations in the active site region

1996 ◽  
Vol 9 (11) ◽  
pp. 997-1003 ◽  
Author(s):  
Péter Bagossi ◽  
Yin-Shyun E. Cheng ◽  
Stephen Oroszlan ◽  
József Tözsér
Keyword(s):  
Active Site ◽  
Active Site Region ◽  
Hiv 1
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