scholarly journals Inhibitory Effect of 2,3,5,6-Tetrafluoro-4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide Derivatives on HIV Reverse Transcriptase Associated RNase H Activities

2016 ◽  
Vol 17 (8) ◽  
pp. 1371 ◽  
Author(s):  
Nicolino Pala ◽  
Francesca Esposito ◽  
Dominga Rogolino ◽  
Mauro Carcelli ◽  
Vanna Sanna ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inhibitory Effect ◽  
Rnase H ◽  
Hiv Reverse Transcriptase

A Homodimeric Sporamin-Type Trypsin Inhibitor with Antiproliferative, HIV Reverse Transcriptase-Inhibitory and Antifungal Activities from Wampee (Clausena lansium) Seeds

2003 ◽  
Vol 384 (2) ◽  
pp. 289-293 ◽  
Author(s):  
T.B. Ng ◽  
S.K. Lam ◽  
W.P. Fong
Keyword(s):  
Reverse Transcriptase ◽  
Trypsin Inhibitor ◽  
Simple Procedure ◽  
Inhibitory Effect ◽  
Exchange Chromatography ◽  
Proteinase K ◽  
Human Leukemia ◽  
Hiv Reverse Transcriptase ◽  
Rabbit Reticulocyte Lysate System ◽  
Reticulocyte Lysate

Abstract A homodimeric trypsin inhibitor with a molecular mass of 54 kDa was isolated from the seeds of Clausena lansium (Lour) Skeels with a very simple procedure comprising extraction with an aqueous buffer and ion exchange chromatography on CM-cellulose. It inhibited trypsin with an IC50 of 2.2 nM but was without any inhibitory effect on chymotrypsin and proteinase K. The uptake of MTT by human leukemia HL60 and hepatoma Hep G2 cells was inhibited with an IC50 of 100 uM. Translation in the cellfree rabbit reticulocyte lysate system was inhibited with an IC50 of 3.6 uM. The activity of HIV-1 reverse transcriptase was reduced in the presence of the trypsin inhibitor. The trypsin inhibitor exerted antifungal activity toward Physalospora piricola but not Mycosphaerella arachidicola, Botrytis cinerea, Fusarium oxysporum or Coprinus comatus.

scholarly journals Effects of the W153L Substitution in HIV Reverse Transcriptase on Viral Replication and Drug Resistance to Multiple Categories of Reverse Transcriptase Inhibitors

2014 ◽  
Vol 58 (8) ◽  
pp. 4515-4526 ◽  
Author(s):  
Hong-Tao Xu ◽  
Susan P. Colby-Germinario ◽  
Maureen Oliveira ◽  
Daniel Rajotte ◽  
Richard Bethell ◽  
...  
Keyword(s):  
Viral Replication ◽  
Reverse Transcriptase ◽  
Rnase H ◽  
Hiv Reverse Transcriptase ◽  
Compound A ◽  
Enzymatic Function ◽  
Biochemical Assays ◽  
Rt Inhibitors ◽  
The Impact ◽  
Hiv 1

ABSTRACTA W153L substitution in HIV-1 reverse transcriptase (RT) was recently identified by selection with a novel nucleotide-competing RT inhibitor (NcRTI) termed compound A that is a member of the benzo[4,5]furo[3,2,d]pyrimidin-2-one NcRTI family of drugs. To investigate the impact of W153L, alone or in combination with the clinically relevant RT resistance substitutions K65R (change of Lys to Arg at position 65), M184I, K101E, K103N, E138K, and Y181C, on HIV-1 phenotypic susceptibility, viral replication, and RT enzymatic function, we generated recombinant RT enzymes and viruses containing each of these substitutions or various combinations of them. We found that W153L-containing viruses were impaired in viral replicative capacity and were hypersusceptible to tenofovir (TFV) while retaining susceptibility to most nonnucleoside RT inhibitors. The nucleoside 3TC retained potency against W153L-containing viruses but not when the M184I substitution was also present. W153L was also able to reverse the effects of the K65R substitution on resistance to TFV, and K65R conferred hypersusceptibility to compound A. Biochemical assays demonstrated that W153L alone or in combination with K65R, M184I, K101E, K103N, E138K, and Y181C impaired enzyme processivity and polymerization efficiency but did not diminish RNase H activity, providing mechanistic insights into the low replicative fitness associated with these substitutions. We show that the mechanism of the TFV hypersusceptibility conferred by W153L is mainly due to increased efficiency of TFV-diphosphate incorporation. These results demonstrate that compound A and/or derivatives thereof have the potential to be important antiretroviral agents that may be combined with tenofovir to achieve synergistic results.

Anti-Aids Agents, 2: Inhibitory Effect of Tannins on HIV Reverse Transcriptase and HIV Replication in H9 Lymphocyte Cells

1990 ◽  
Vol 53 (3) ◽  
pp. 587-595 ◽  
Author(s):  
Gen-ichiro Nonaka ◽  
Itsuo Nishioka ◽  
Makoto Nishizawa ◽  
Takashi Yamagishi ◽  
Yoshiki Kashiwada ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Inhibitory Effect ◽  
Hiv Reverse Transcriptase ◽  
Hiv Replication

1′,5′-Anhydrohexitol Oligonucleotides: Hybridisation and Strand Displacement with Oligoribonucleotides, Interaction with RNase H and HIV Reverse Transcriptase

1997 ◽  
Vol 3 (9) ◽  
pp. 1513-1520 ◽  
Author(s):  
Chris Hendrix ◽  
Helmut Rosemeyer ◽  
Bart De Bouvere ◽  
Arthur Van Aerschot ◽  
Frank Seela ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Rnase H ◽  
Strand Displacement ◽  
Hiv Reverse Transcriptase

scholarly journals Nucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse Transcriptase

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Moisés A. Árquez ◽  
Samara Martín-Alonso ◽  
Robert J. Gorelick ◽  
Walter A. Scott ◽  
Antonio J. Acosta-Hoyos ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Nucleocapsid Protein ◽  
Inhibitory Effect ◽  
Rnase H ◽  
Resistance Mutations ◽  
Site Mutation ◽  
Development Of Resistance ◽  
Transcription Process ◽  
Dna Primers ◽  
Hiv 1

ABSTRACT In HIV-1, development of resistance to AZT (3′-azido-3′-deoxythymidine) is mediated by the acquisition of thymidine analogue resistance mutations (TAMs) (i.e., M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q) in the viral reverse transcriptase (RT). Clinically relevant combinations of TAMs, such as M41L/T215Y or D67N/K70R/T215F/K219Q, enhance the ATP-mediated excision of AZT monophosphate (AZTMP) from the 3′ end of the primer, allowing DNA synthesis to continue. Additionally, during HIV-1 maturation, the Gag polyprotein is cleaved to release a mature nucleocapsid protein (NCp7) and two intermediate precursors (NCp9 and NCp15). NC proteins interact with the viral genome and facilitate the reverse transcription process. Using wild-type and TAM-containing RTs, we showed that both NCp9 and NCp15 inhibited ATP-mediated rescue of AZTMP-terminated primers annealed to RNA templates but not DNA templates, while NCp7 had no effect on rescue activity. RNase H inactivation by introducing the active-site mutation E478Q led to the loss of the inhibitory effect shown by NCp9. NCp15 had a stimulatory effect on the RT’s RNase H activity not observed with NCp7 and NCp9. However, analysis of RNase H cleavage patterns revealed that in the presence of NCp9, RNA/DNA complexes containing duplexes of 12 bp had reduced stability in comparison with those obtained in the absence of NC or with NCp7 or NCp15. These effects are expected to have a strong influence on the inhibitory action of NCp9 and NCp15 by affecting the efficiency of RNA-dependent DNA polymerization after unblocking DNA primers terminated with AZTMP and other nucleotide analogues.

scholarly journals Design, Synthesis, and Biological Evaluations of Hydroxypyridonecarboxylic Acids as Inhibitors of HIV Reverse Transcriptase Associated RNase H

2016 ◽  
Vol 59 (10) ◽  
pp. 5051-5062 ◽  
Author(s):  
Jayakanth Kankanala ◽  
Karen A. Kirby ◽  
Feng Liu ◽  
Lena Miller ◽  
Eva Nagy ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Rnase H ◽  
Hiv Reverse Transcriptase ◽  
Design Synthesis

Functional characterization of RNA-dependent DNA polymerase and RNase H activities of a recombinant HIV reverse transcriptase

Biochemistry ◽  
1991 ◽  
Vol 30 (10) ◽  
pp. 2651-2655 ◽  
Author(s):  
Cheng Keat Tan ◽  
Jian Zhang ◽  
Zhao Yan Li ◽  
W. Gary Tarpley ◽  
Kathleen M. Downey ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Dna Polymerase ◽  
Functional Characterization ◽  
Rnase H ◽  
Hiv Reverse Transcriptase
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