The Biological Effects of Structural Variation at the Meta Position of the Aromatic Rings and at the End of the Alkenyl Chain in the Alkenyldiarylmethane Series of Non-Nucleoside Reverse Transcriptase Inhibitors

2001 ◽  
Vol 44 (24) ◽  
pp. 4092-4113 ◽  
Author(s):  
Guozhang Xu ◽  
Mark Micklatcher ◽  
Maximilian A. Silvestri ◽  
Tracy L. Hartman ◽  
Jennifer Burrier ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Structural Variation ◽  
Biological Effects ◽  
Aromatic Rings ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Meta Position ◽  
Alkenyl Chain

Insights into Biophysical Methods to Study Interactions Between HIV-1 Reverse Transcriptase and Non-nucleoside Reverse Transcriptase Inhibitors

2020 ◽  
Vol 17 (6) ◽  
pp. 818-825
Author(s):  
Julien Dumond ◽  
Jean-Marcel Julien Tronchet ◽  
Serge Kirkiacharian ◽  
Michel Seman ◽  
Michèle Reboud-Ravaux
Keyword(s):  
Reverse Transcriptase ◽  
Biological Effects ◽  
Tryptophan Fluorescence ◽  
Plasmonic Resonance ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Surface Plasmonic Resonance ◽  
Rt Inhibitors ◽  
Hiv 1

Background: Reverse Transcriptase (RT) of immunodeficiency virus type-1 (HIV-1) remains an essential target for new antiretroviral therapies. Non-nucleoside reverse transcriptase inhibitors (or NNRTIs) constitute a major class of RT inhibitors whose characterization is essential. Introduction: Several biochemical, biological, and biophysical methods have been previously used to analyze the biological effects of NNRTIs. We explored here the use of surface plasmonic resonance to characterize the affinity of RT towards selected NNRTIs and compared the results with those obtained with in vitro and in cellulo assays. Methods: The solubility and stability in buffers of the tested NNRTIs were assessed by spectrophotometry and fluorescence. Surface plasmonic resonance experiments to study direct NNRTIs binding to immobilized RT and intramolecular quenching of RT tryptophan fluorescence were used to determine the KA association constants (= 1/KD) between RT and the inhibitors. The in vitro inhibition constants of RT were determined using kinetics and the effects on three other potential targets (proteasome, HIV-1 integrase, and HIV-1 protease) were analyzed. Results: The results obtained with two typical molecules belonging to our previous N-hydroxyureido acylnucleoside derivatives series using the above biophysical assays matched those obtained in in vitro and previous in cellulo assays. Conclusion: Surface plasmonic resonance provides reliable thermodynamic information on the interaction of RT with NNRTIs and appears as a useful method for understanding their inhibitory mechanism.

scholarly journals An insight on promising strategies hoping to cure HIV-1 infection by targeting Rev protein—short review

2021 ◽  
Author(s):  
Sahana Pai ◽  
Jayesh Mudgal ◽  
B. Venkatesh Kamath ◽  
K. Sreedhara Ranganath Pai
Keyword(s):  
Reverse Transcriptase ◽  
Regulatory Protein ◽  
Short Review ◽  
Fixed Dose ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Promising Therapeutic Target ◽  
Latent Hiv ◽  
Approved Drugs ◽  
Hiv 1

AbstractHuman immunodeficiency virus-1 (HIV-1) infection remains to be one of the major threats throughout the world. Many researchers are working in this area to find a cure for HIV-1. The group of the FDA approved drugs which are currently used against HIV-1 in the clinical practice include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (InIs), and protease inhibitors (PIs). Fixed dose combinations (FDCs) of these drugs are available and are used as per the anti-retroviral therapy (ART) guidelines. Despite these, unfortunately, there is no cure for HIV1 infection to date. The present review is focused upon describing the importance of a post-transcriptional regulatory protein “Rev”, responsible for latent HIV-1 infection as a possible, and promising therapeutic target against HIV-1.

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