Human immunodeficiency virus reverse transcriptase HIV-RT

In studies of molecular simplification of catechins targeting both human immunodeficiency virus reverse transcriptase (HIV-RT) and mutated EHV-RT enzymes, we are able to differentiate the polymerase and strand-transfer inhibiting activities... 

A potent specific telomerase inhibitor designated as telomestatin, 363, was isolated from Streptomyces anulatus 3533-SV4 <2001JA1262>. Although telomerase consists of several components with DNA polymerase or reverse transcriptase activity in addition to its intrinsic telomerase component, telomestatin specifically inhibited telomerase without affecting DNA polymerase and human immunodeficiency virus-reverse transcriptase (HIV-RT). 

A novel antifungal protein, designated chrysancorin, was isolated from the seeds of Chrysanthemum coronarium var. spatiosum LH Bailey [259]. It inhibits the activity of human immunodeficiency virus-reverse transcriptase (HIV-RT). The protein also possesses antifungal activity towards Botrytis cinerea, Mycosphaerella arachidicola and Physalospora piricola, but not against Rhizoctonum solani, Fusarium oxysporum, Coprinus comatus and a variety of bacteria tested. 

Fig. 5.7. Activation, incorporation, and chain-terminating action of azidothymidine (AZT), a thymidine analogue, as a reversible inhibitor of human immunodeficiency virus-reverse transcriptase (HIV-RT).

HIV-RT = Human Immunodeficiency Virus- Reverse Transcriptase ACKNOWLEDGEMENTS... 

Kleim JP, ROsner M, Winkler I, Paessens A, Kirsch R, Hsiou Y, Arnolds E, Riess G (1996) Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74 -> Val or He and Val-75 - > Leu or He) HIV-1 mutants, Proc Natl Acad Sci USA 93 34-38... 

I, Umezu K, Walker RT, Mori S, Ito M, Shigeta S, Miyasaka T. Potent and selective inhibition of human immunodeficiency virus type 1 (HIV-1) by 5-ethyl-6-phenylthiouracil derivatives through their interaction with the HIV-1 reverse transcriptase. Proc Natl Acad Sci USA 1991 88 2356-2360. 

The rapid spread of acquired immune deficiency syndrome (AIDS) has prompted numerous efforts to develop therapeutic agents against the human immunodeficiency virus type 1 (HIV-1) [2351. Efforts have focused on inhibition of the virally encoded reverse transcriptase (RT) enzyme, which is responsible for the conversion of retroviral RNA to proviral DNA. The nucleoside RT inhibitors 3 -azidothymidine (AZT) and dideoxyinosine (ddl) have proven to be clinically useful anti HIV-1 agents [236], but due to their lack of selectivity versus other DNA polymerases, these compounds are flawed by their inherent toxi-... 

Like all other retroviruses, human immunodeficiency virus type 1 (HIV-1) contains the multifunctional enzyme reverse transcriptase (RT). Retroviral RTs have a DNA polymerase activity that can use either an RNA or a DNA template and an RNase H activity. HIV-1 RT is essential for the conversion of single-stranded viral RNA into a linear double-stranded DNA that is subsequently integrated into the host cell chromosomes [1-4]. In this conversion process HIV-1 RT catalyzes the incorporation of approximately... 

In the next peiragraph, we describe our work on the meiin targets for therapeutic intervention in AIDS, the enzymes protease and reverse transcriptase from human immunodeficiency virus type 1 (HIV-1 PR and HIV-1 RT). Subsequently, we focus on an... 

The human immunodeficiency virus type 1 (HIV-1) belongs to the family of positive-stranded, enveloped RNA viruses with a DNA intermediate step (retroviruses). Because of the lack of fidelity of the reverse transcriptase (RT), the replication is error-prone, and the infection is characterized by its quasispecies nature. Antiretroviral treatment with such compounds as zidovudine (AZT), zalcitabine (ddC), didanosine (ddl), stavudine (d4T), and lamivudine (3TC) select for quasispecies variants that are resistant to these compounds (1). The detection of these variants is clinically important because they may affect the outcome of the treatment (2). 

Reverse transcriptase (RT) plays a critical role in the early steps of the life of human immunodeficiency virus (HIV) (304), and for over a decade has been one of the major targets of AIDS therapy. Polycitone A (280) was found to be a potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerases (305). Polycitone A exhibited potent inhibitory capacity of both RNA- and DNA-directed DNA polymerases. It inhibits retroviral reverse transcriptases (RTs) of human immunodeficiency virus type 1 (HIV), murine leukemia virus (MLV) and mouse mammary tumor virus (MMTV)] as efficiently as cellular DNA polymerases of both DNA polymerases a and p and the prokaryotic Klenow fragment of Escherichia coli DNA polymerase I. The mode and mechanism of inhibition of the DNA-polymerase activity associated with HIV-1 RT by polycitone A (280) have been studied. The results suggest that the inhibitory capacity of the DNA polymerase activity is independent of the template-primer used. The RNase H function is hardly affected by this inhibitor. Polycitone A has been shown to interfere with DNA primer extension, as well as with the formation of the RT-DNA complex. Steady-state kinetic studies demonstrate that this inhibitor can be considered as an allosteric inhibitor of HIV-1 RT. The target site on the enzyme may be also spatially related to the... 

De Clercq E. HIV-1-specific RT inhibitors highly selective inhibitors of human immunodeficiency virus type 1 that are specifically targeted at the viral reverse transcriptase. Med Res Rev 1993 13 229—258. 

Up to this point, GIPF expressions have been formulated for only one type of biological activity - the inhibition of reverse transcriptase (RT), the enzyme that promotes the reverse transcription of genomic RNA into double-stranded DNA, a key step in the replication of the human immunodeficiency virus, HIV [82, 87]. Analytical representations were obtained for the anti-HIV potencies of three families of RT inhibitors the correlation coefficients are between 0.930 and 0.952. We are currently investigating the effects of applying the GIPF approach to certain portions of the molecules rather than their entireties. This might reveal the source of the activity, or alternatively, indicate it to be delocalized. 

The detection of HIV-related proteins is one of the most challenging tasks. This is especially true because AIDS should be diagnosed as early as possible to enable an early and effective therapy of this infection. Pavski and Le (57) used the aptamer strategy to detect reverse transcriptase (RT) of the type 1 human immunodeficiency virus (HIV-1). A direct and specific ACE method was proposed using laser-induced fluorescence (ACE/LIF) as detection principle. Single-stranded DNA aptamers as probes fluorescently labeled were synthesized. The resulting aptamer is specific for HIV-1 RT, and it exhibited no cross-reactivity with RTs of the enhanced avian myeloblastosis virus (AMV), the Moloney murine leukemia virus (MMLV), or denatured HIV-1 RT. An affinity complex of RT 26-HIV-l RT was stable, with calibration curves linear up to 50 nM (6 /xg/mL) HIV-1 RT concentration. Both... 

A recent example is the substrate analogue thymidine 5 -[a,P-imido]triphosphate [141171-20-2] (TMPNPP) (2) which competitively inhibits the human immunodeficiency virus-1 (HIV-1) reverse transcriptase (HIV-1 RT) with a K value of 2.4 micromolar ( TM) (9). The substrate is thymidine 5 -triphosphate... 

In a more recent continuation of these studies, Campiani and co-workers carried out semi-empirical calculations on a series of active compounds related to 2. This led to the identification of several structural and conformational features responsible for this activity <2005JME4367>. Docking into the human immunodeficiency virus 1 (HIV-1) reverse transcriptase non-nucleotide binding site (RT NNBS) of a compound of type 3 (X = O) highlighted that one of the phenyl rings of this compound protrudes toward the catalytic site <2005JME7153>. 

Cys202 [208]. Human immunodeficiency virus (HIV) is the primary cause of acquired immunodeficiency syndrome (AIDS). In an effort to find new drugs preventing the growth of HIV, Masao et al developed an in vitro assay method of RNase H activity associated with reverse transcriptase (RT) from HIV-1. Some 1,4-naphthoquinones moderately inhibited RNase H activity [209]. Several natural occurring naphtoquinones have showed antiretroviral activity [210-211],... 

HISK, histidine-specific protein kinase HIS-R, histamine receptor HIV-1, human immunodeficiency virus 1 HIV-1 IN, HIV-1 integrase HIV-1 PR, HIV-1 protease HIV-1 RT, HIV-1 reverse transcriptase HMG protein, high mobility group protein... 

HIV-1 RT = Human Immunodeficiency Virus-type 1 Reverse Transcriptase... 

This table is intended to hold results of assays testing compounds in reg-istry.structure for activity as human immunodeficiency virus (HIV) protease inhibitors. As new assays are added, the test results can be added to newly created tables with similar definitions. For example, there might be tables for HIV reverse transcriptase inhibitors stored in a table named hiv.rt. Other assay results might be stored in new schemas, for example, fpr.htfc for high-throughput flow cytometry results for the formyl peptide receptor (FPR), or f pr.ca for FPR cell adhesion assay results. Each of these tables would have columns of data named and typed appropriately for each assay. Each table would have a column containing a compound id that references compounds in the registry, structure table. 

Retroviruses are eukaryotic RNA-viruses, such as certain tumor viruses and human immunodeficiency virus (HIV) containing an RNA-directed DNA polymerase (reverse transcriptase, RT). Viral reverse transcriptase is a multifunctional enzyme possessing three enzymatic activities, which catalyze reactions essential to viral replication (Skalka and Goff, 1993) ... 

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