Crystal Structures for HIV-1 Reverse Transcriptase in Complexes with Three Pyridinone Derivatives:  A New Class of Non-Nucleoside Inhibitors Effective against a Broad Range of Drug-Resistant Strains

2005 ◽  
Vol 48 (24) ◽  
pp. 7582-7591 ◽  
Author(s):  
Daniel M. Himmel ◽  
Kalyan Das ◽  
Arthur D. Clark, ◽  
Stephen H. Hughes ◽  
Abdellah Benjahad ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Crystal Structures ◽  
Drug Resistant ◽  
New Class ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Nucleoside Inhibitors ◽  
Hiv 1

Evaluation of 4-thiazolidinone derivatives as potential reverse transcriptase inhibitors against HIV-1 drug resistant strains

2017 ◽  
Vol 71 ◽  
pp. 211-218 ◽  
Author(s):  
Rahul Suryawanshi ◽  
Sushama Jadhav ◽  
Nandini Makwana ◽  
Dipen Desai ◽  
Devidas Chaturbhuj ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Drug Resistant ◽  
Reverse Transcriptase Inhibitors ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Hiv 1

scholarly journals Oxazole-Benzenesulfonamide Derivatives Inhibit HIV-1 Reverse Transcriptase Interaction with Cellular eEF1A and Reduce Viral Replication

2019 ◽  
Vol 93 (12) ◽  
Author(s):  
Daniel J. Rawle ◽  
Dongsheng Li ◽  
Zhonglan Wu ◽  
Lu Wang ◽  
Marcus Choong ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Small Molecule ◽  
Reverse Transcription ◽  
Dependent Manner ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Dose Dependent ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Transcription And Replication

ABSTRACT HIV-1 replication requires direct interaction between HIV-1 reverse transcriptase (RT) and cellular eukaryotic translation elongation factor 1A (eEF1A). Our previous work showed that disrupting this interaction inhibited HIV-1 uncoating, reverse transcription, and replication, indicating its potential as an anti-HIV-1 target. In this study, we developed a sensitive, live-cell split-luciferase complementation assay (NanoBiT) to quantitatively measure inhibition of HIV-1 RT interaction with eEF1A. We used this to screen a small molecule library and discovered small-molecule oxazole-benzenesulfonamides (C7, C8, and C9), which dose dependently and specifically inhibited the HIV-1 RT interaction with eEF1A. These compounds directly bound to HIV-1 RT in a dose-dependent manner, as assessed by a biolayer interferometry (BLI) assay, but did not bind to eEF1A. These oxazole-benzenesulfonamides did not inhibit enzymatic activity of recombinant HIV-1 RT in a homopolymer assay but did inhibit reverse transcription and infection of both wild-type (WT) and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 in a dose-dependent manner in HEK293T cells. Infection of HeLa cells was significantly inhibited by the oxazole-benzenesulfonamides, and the antiviral activity was most potent against replication stages before 8 h postinfection. In human primary activated CD4+ T cells, C7 inhibited HIV-1 infectivity and replication up to 6 days postinfection. The data suggest a novel mechanism of HIV-1 inhibition and further elucidate how the RT-eEF1A interaction is important for HIV-1 replication. These compounds provide potential to develop a new class of anti-HIV-1 drugs to treat WT and NNRTI-resistant strains in people infected with HIV. IMPORTANCE Antiretroviral drugs protect many HIV-positive people, but their success can be compromised by drug-resistant strains. To combat these strains, the development of new classes of HIV-1 inhibitors is essential and a priority in the field. In this study, we identified small molecules that bind directly to HIV-1 reverse transcriptase (RT) and inhibit its interaction with cellular eEF1A, an interaction which we have previously identified as crucial for HIV-1 replication. These compounds inhibit intracellular HIV-1 reverse transcription and replication of WT HIV-1, as well as HIV-1 mutants that are resistant to current RT inhibitors. A novel mechanism of action involving inhibition of the HIV-1 RT-eEF1A interaction is an important finding and a potential new way to combat drug-resistant HIV-1 strains in infected people.

Rates of transmission of antiretroviral drug resistant strains of HIV-1

2003 ◽  
Vol 26 (2) ◽  
pp. 153-161 ◽  
Author(s):  
Palanee Ammaranond ◽  
Philip Cunningham ◽  
Robert Oelrichs ◽  
Kazuo Suzuki ◽  
Claire Harris ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Antiretroviral Drug ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Hiv 1

scholarly journals R88-APOBEC3Gm Inhibits the Replication of Both Drug-resistant Strains of HIV-1 and Viruses Produced From Latently Infected Cells

2014 ◽  
Vol 3 ◽  
pp. e151 ◽  
Author(s):  
Xiaoxia Wang ◽  
Zhujun Ao ◽  
Kallesh Danappa Jayappa ◽  
Bei Shi ◽  
Gary Kobinger ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Latently Infected ◽  
Infected Cells ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Hiv 1

Low rate of genotypic HIV-1 drug-resistant strains in the Senegalese government initiative of access to antiretroviral therapy

AIDS ◽  
2003 ◽  
Vol 17 ◽  
pp. S31-S38 ◽  
Author(s):  
Laurence Vergne ◽  
Coumba Touré Kane ◽  
Christian Laurent ◽  
Ndella Diakhaté ◽  
Ndeye Fatou Ngom Gueye ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Government Initiative ◽  
Drug Resistant Strains ◽  
Hiv 1 ◽  
Low Rate

Slow-, Tight-Binding HIV-1 Reverse Transcriptase Non-Nucleoside Inhibitors Highly Active against Drug-Resistant Mutants

ChemMedChem ◽  
2007 ◽  
Vol 2 (4) ◽  
pp. 445-448 ◽  
Author(s):  
Reynel Cancio ◽  
Antonello Mai ◽  
Dante Rotili ◽  
Marino Artico ◽  
Gianluca Sbardella ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Tight Binding ◽  
Drug Resistant ◽  
Highly Active ◽  
Resistant Mutants ◽  
Nucleoside Inhibitors ◽  
Hiv 1

scholarly journals Estimation of the HIV-1 backward mutation rate from transmitted drug-resistant strains

2016 ◽  
Vol 112 ◽  
pp. 33-42 ◽  
Author(s):  
J.M. Kitayimbwa ◽  
J.Y.T. Mugisha ◽  
R.A. Saenz
Keyword(s):  
Mutation Rate ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Hiv 1

Synthesis and evaluation of potent human immunodeficiency virus 1 protease inhibitors with epimeric isopropanol as novel P1′ ligands

2020 ◽  
Vol 12 (9) ◽  
pp. 775-794 ◽  
Author(s):  
Mei Zhu ◽  
Ling Ma ◽  
Biao Dong ◽  
Guoning Zhang ◽  
Juxian Wang ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Design Strategy ◽  
Drug Resistant ◽  
Inhibition Activity ◽  
Protease Enzyme ◽  
Immunodeficiency Virus ◽  
Resistant Strains ◽  
Backbone Atoms ◽  
Drug Resistant Strains ◽  
Hiv 1

Aim: HIV-1 protease inhibitors regimens suffered from a number of drawbacks, among which, the most egregious issue was the growing emergence of drug-resistant strains. Materials & methods: The design strategy of maximizing the protease active site interactions with the inhibitor, especially promoting extensive hydrogen bonding with the protein backbone atoms, might be in favor of combating drug resistance. A series of HIV-1 protease inhibitors that incorporated enantiomeric isopropanols as the P1′ ligands in combination with phenols as the P2 ligands were reported herein. Results: A number of inhibitors displayed potent protease enzyme inhibition activity. In particular, inhibitor 14c showed comparable potency as darunavir with IC50 value of 1.91 nM and activity against darunavir-resistant HIV-1 variants. Conclusion: The new kind of HIV-1 protease inhibitors deserves further study.

Prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients who have rebound in viral load while receiving antiretroviral therapy in the UNAIDS–Drug Access Initiative in Abidjan, Côte dʼIvoire

AIDS ◽  
2003 ◽  
Vol 17 ◽  
pp. S23-S29 ◽  
Author(s):  
Christiane Adjé-Touré ◽  
Bilé Celestin ◽  
Debra Hanson ◽  
Thierry H. Roels ◽  
Kurt Hertogs ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Drug Resistant ◽  
Drug Access ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Hiv 1
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