Roles of Conformational and Positional Adaptability in Structure-Based Design of TMC125-R165335 (Etravirine) and Related Non-nucleoside Reverse Transcriptase Inhibitors That Are Highly Potent and Effective against Wild-Type and Drug-Resistant HIV-1 Variants

2004 ◽  
Vol 47 (10) ◽  
pp. 2550-2560 ◽  
Author(s):  
Kalyan Das ◽  
Arthur D. Clark, ◽  
Paul J. Lewi ◽  
Jan Heeres ◽  
Marc R. de Jonge ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1

scholarly journals HIV Drug Resistance Mutations in Patients with HIV and HIV-TB Coinfection After Failure of First-Line Therapy: A Prevalence Study in a Resource-Limited Setting

2019 ◽  
Vol 18 ◽  
pp. 232595821984906
Author(s):  
Nawaid Hussain Khan ◽  
Mikashmi Kohli ◽  
Kartik Gupta ◽  
Bimal Kumar Das ◽  
Ravindra Mohan Pandey ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
First Line Therapy ◽  
Resource Limited ◽  
High Prevalence ◽  
Hiv 1 ◽  
Limited Setting

Introduction: The present study aimed to report the prevalent HIV-1 drug-resistant mutations in patients with HIV-1 alone and tuberculosis (TB) coinfection alone to improve our understanding of the mutation patterns and aid treatment decisions. Methods: Patients with HIV-1 and HIV-TB on treatment for more than 1 year with suspected failure were recruited. Sequencing of protease and two-thirds of the region of reverse transcriptase gene was done for drug-resistant mutations. Results: In the HIV-TB group (n = 25), 88%, 92%, and 12% had mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs), respectively. In the HIV-alone group (n = 25), 84%, 100%, and 4% had mutations to NRTIs, NNRTIs, and PIs, respectively. M184V, M41L, D67N, G190A, A98G, and K103N were the most common mutations seen. Conclusion: There is a high prevalence of drug-resistant mutations in HIV and HIV-TB coinfected patients.

scholarly journals Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1581
Author(s):  
Ting-Ting Li ◽  
Christophe Pannecouque ◽  
Erik De Clercq ◽  
Chun-Lin Zhuang ◽  
Fen-Er Chen
Keyword(s):  
Reverse Transcriptase ◽  
Scaffold Hopping ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Single Digit ◽  
Hydrophobic Cavity ◽  
Structure Activity ◽  
Anti Hiv ◽  
Hiv 1

Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC50 = 6 nM) and B6 (EC50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 μM). The preliminary structure–activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.

Discovery of Novel Benzimidazolones as Potent Non-Nucleoside Reverse Transcriptase Inhibitors Active Against Wild-Type and Mutant HIV-1 Strains.

ChemInform ◽  
2007 ◽  
Vol 38 (34) ◽  
Author(s):  
Maria Letizia Barreca ◽  
Angela Rao ◽  
Laura De Luca ◽  
Nunzio Iraci ◽  
Anna-Maria Monforte ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1

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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