The influence of natural substrates and inhibitors on the nucleotide-dependent excision activity of HIV-1 reverse transcriptase in the infected cell.

Abstract:

:Human immunodeficiency virus type 1 resistance to nucleoside reverse transcriptase inhibitors such as 3'-azido-2', 3'-dideoxythymidine (AZT) can arise through mutations in the coding region of reverse transcriptase (RT) that enhance the enzyme's ability to remove the drug after it has been incorporated. This excision activity of HIV-1 RT has been well characterized in a number of in vitro systems. However, the in vitro findings do not provide a complete picture of the in vivo significance of this resistance mechanism. This review will attempt to bridge the gap between the in vitro observations and the in vivo environment by summarizing the fragmentary information that is available about the intracellular conditions that may influence drug excision in cell subpopulations that are infected by HIV-1. Topics that will be discussed include (a) intracellular compounds HIV-1 RT may use to remove chain terminators; (b) how dNTPs can affect excision activity and how these effects differ in different immune cell subpopulations; (c) the influence of HIV infection on excision activity--e.g., through immune activation of infected cells or through changes indirectly induced in cells that subsequently become infected; (d) intracellular conditions that favor selection for mutations that increase the excision-based resistance mechanism; (e) the importance of macrophages in the selection of resistance mutations. Understanding factors that control excision in the intracellular environment will greatly enhance our understanding of the process of selection for this class of drug resistance mutations and may open doors for the development of novel targets for antiviral therapy.

journal_name

Curr Pharm Des

authors

Smith AJ,Scott WA

doi

10.2174/138161206776873572

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

1827-41

issue

15

eissn

1381-6128

issn

1873-4286

journal_volume

12

pub_type

杂志文章,评审
  • Pituitary Adenylyl Cyclase Activating Polypeptide (PACAP) Signaling and the Cell Cycle Machinery in Neurodegenerative Diseases.

    abstract::Pituitary adenylyl cyclase activating polypeptide (PACAP) is a neuropeptide with great neuroprotective effects and remarkable therapeutic potential. PACAP activates several cellular pathways to exert its protective effects. Emerging evidence shows that PACAP can modify the levels and activity of cell cycle components ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612825666181127102311

    authors: Polanco MJ,Pennuto M

    更新日期:2018-01-01 00:00:00

  • Locked nucleic acid holds promise in the treatment of cancer.

    abstract::Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ra...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161208784246234

    authors: Frieden M,Ørum H

    更新日期:2008-01-01 00:00:00

  • Role of Colloidal Drug Delivery Carriers in Taxane-mediated Chemotherapy: A Review.

    abstract::Chemotherapy is one of the most frequently employed and reliable treatment options for the management of a variety of cancers. Taxanes (paclitaxel, docetaxel and cabazitaxel) are frequently prescribed to treat breast cancer, hormone refractory prostate cancer, non-small cell lung cancer and ovarian cancer. Most of the...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666160524144926

    authors: Kumar P,Raza K,Kaushik L,Malik R,Arora S,Katare OP

    更新日期:2016-01-01 00:00:00

  • Polysaccharide Colloids as Smart Vehicles in Cancer Therapy.

    abstract::Cancer disease is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and around 8 million cancer-related deaths yearly. Estimates expect to increase these figures over the next few years. Therefore, it is very important to develop more effective and targeted therapi...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612821666150820100812

    authors: Caro C,Pozo D

    更新日期:2015-01-01 00:00:00

  • Clinical PET imaging of insulinoma and beta-cell hyperplasia.

    abstract::Persistent hyperinsulinemic hypoglycemia (PHH) is caused by solitary benign insulinoma or hyperplasia of pancreatic beta cells. In infants, PHH is caused by functionally defective hyperplastic beta cells, which are either diffusely or focally distributed in the pancreas. In adults, insulinoma is the most common cause ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210791164090

    authors: Kauhanen S,Seppänen M,Minn H,Nuutila P

    更新日期:2010-05-01 00:00:00

  • Barriers to Risk Stratification Accuracy in Ischemic Heart Disease in Women: The Role of Non-Obstructive Coronary Artery Disease.

    abstract:BACKGROUND:A substantial part of literature has been centered on sex differences in the clinical aspects of ischemic heart disease (IHD). Many reports have documented differences in the presentation and risk profile between women and men. Such differences drive sex-related inequalities in the referral and treatment of ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666160311115344

    authors: Cenko E,Bugiardini R

    更新日期:2016-01-01 00:00:00

  • Clopidogrel resistance: implications for coronary stenting.

    abstract::Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clop...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206776361345

    authors: Gurbel PA,Lau WC,Bliden KP,Tantry US

    更新日期:2006-01-01 00:00:00

  • The effect of Endovascular Aneurysm Repair on Renal Function in Patients Treated for Abdominal Aortic Aneurysm.

    abstract:AIM:The effect of endovascular aneurysm repair in patients treated for abdominal aortic aneurysm has not been clearly defined. The objective of the present article was to provide a contemporary literature review and perform an analysis to determine the effect of EVAR on renal function in the early post-operative period...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612825666191129094923

    authors: Nana P,Kouvelos G,Brotis A,Spanos K,Giannoukas A,Matsagkas M

    更新日期:2019-01-01 00:00:00

  • Design of multivalent ligand targeting G-protein-coupled receptors.

    abstract::More and more evidences are still accumulating rapidly on the G-protein-coupled-receptors (GPCRs) dimerization/oligomerization. Such common feature of GPCRs has called extensive attention to both pharmacologists and medicinal chemists for illustration of the pharmacological functions and therapeutic utilities of such ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161209787315639

    authors: Liu Z,Zhang J,Zhang A

    更新日期:2009-01-01 00:00:00

  • Neuroinflammation: A Therapeutic Target of Cotinine for the Treatment of Psychiatric Disorders?

    abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161282210160304112511

    authors: Echeverria V,Grizzell JA,Barreto GE

    更新日期:2016-01-01 00:00:00

  • Aging and Autism: Understanding, Intervention and Proposals to Improve Quality of Life.

    abstract:BACKGROUND:The population with autism spectrum disorder (ASD) has been increasing and is currently estimated to be 1 in 58 births. The increased prevalence of ASD together with the lack of knowledge on the processes of aging in this population, the support needed at this stage of life, and the associated risk factors, ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612825666191204165117

    authors: Ruggieri V,Gómez JLC,Martínez MM,Arberas C

    更新日期:2019-01-01 00:00:00

  • Synergistic effect of inhibitors of MMPs and ROS-dependent modifications of contractile proteins on protection hearts subjected to oxidative stress.

    abstract::Cardiac ischemia, followed by reperfusion, often results in the development of cardiac contractile dysfunction that limits the recovery prognosis of patients. The current goal of pharmacological therapy in the course of ischemic heart disease is to improve the oxygen supply/demand ratio for the heart. Cardiac contract...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/13816128113199990556

    authors: Sawicki G

    更新日期:2014-01-01 00:00:00

  • Rheumatoid arthritis: genetic variants as biomarkers of cardiovascular disease.

    abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature mortality, severe morbidity, and functional impairment leading to considerable financial burden for both patients and society. Since disease progression and complications can differ from one patient to another, genetic markers are of...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612820666140825123407

    authors: Rodriguez-Rodriguez L,López-Mejias R,Fernández-Gutiérrez B,Balsa A,González-Gay MA,Martín J

    更新日期:2015-01-01 00:00:00

  • Inhibitors of HIV-1 entry.

    abstract::Since the discovery of human immunodeficiency virus (HIV) as a causative agent of acquired immune deficiency syndrome (AIDS) various strategies were employed to counter its devastating actions. One such concept relies on the prevention of HIV entry into host's "competent" cells by means of compounds known as entry inh...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811319100003

    authors: Micewicz ED,Ruchala P

    更新日期:2013-01-01 00:00:00

  • Regulation of GABA Neurotransmission by Glutamic Acid Decarboxylase (GAD).

    abstract::Control of GABA neurotransmission at the pre-synaptic site occurs substantially through the activation of the glutamic acid decarboxylase (GAD) enzymes GAD65 and GAD67. Concentrations of GAD65 and GAD67 are controlled either by transcription or by mRNA splicing and importantly the activities of these key enzymes are r...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612821666150917094343

    authors: Modi JP,Prentice H,Wu JY

    更新日期:2015-01-01 00:00:00

  • Targeting the cell cycle in the pursuit of novel chemotherapies against parasitic protozoa.

    abstract::Protozoan parasites, such as those responsible for malaria and African Sleeping Sickness, represent a huge burden to the developing world. Current chemotherapy to combat these diseases is inadequate: antiquated, toxic and increasingly ineffective due to drug resistance. In this article, the potential usefulness of tar...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161208784041042

    authors: Grant KM

    更新日期:2008-01-01 00:00:00

  • Global Effects of Early Life Stress on Neurons and Glial Cells.

    abstract::Early life stress is considered a risk factor for the development of many diseases in both adolescence and adulthood. It has been reported that chronic stress (for instance, due to maternal separation during breast feeding), causes damage to the central nervous system at the level of neurons and glial cells, which are...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612823666170224111641

    authors: Duenas Z,Caicedo-Mera JC,Torner L

    更新日期:2018-02-12 00:00:00

  • Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists in experimental myocarditis.

    abstract::Myocarditis is a disease whose pathogenesis is not completely understood and whose prevalence is likely underestimated. Individuals afflicted with this condition may be treated with agents that relieve symptoms arising from inflammation and concurrent cellular damage. One class of drugs commonly used in the treatment ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612033455440

    authors: Godsel LM,Leon JS,Engman DM

    更新日期:2003-01-01 00:00:00

  • Targeting IL-23 and Th17-cytokines in inflammatory bowel diseases.

    abstract::Over the last 15 years, the use of various biological therapies has largely improved the way we manage patients with Inflammatory Bowel Diseases (IBDs). Blockade of cytokine synthesis and/or activity is at the forefront of this new era with the success of inhibitors of tumor necrosis factor (TNF)-α. These therapies ar...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210794079164

    authors: De Nitto D,Sarra M,Cupi ML,Pallone F,Monteleone G

    更新日期:2010-01-01 00:00:00

  • Glucose metabolism and insulin resistance in sepsis.

    abstract::Hyperglycemia is a common feature of the critically ill in general and of patients with sepsis in particular. Even a moderate degree of hyperglycemia appears detrimental for the outcome of critically ill patients, since maintenance of normoglycemia (blood glucose levels

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161208784980563

    authors: Van Cromphaut SJ,Vanhorebeek I,Van den Berghe G

    更新日期:2008-01-01 00:00:00

  • Microdialysis in neurointensive care.

    abstract::Microdialysis is a technique for sampling the chemistry of the interstitial fluid of tissues and organs in animal and man. It is minimally invasive and simple to perform in a clinical setting. Although microdialysis samples essentially all small molecular substances present in the interstitial fluid the use of microdi...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612043384105

    authors: Ungerstedt U,Rostami E

    更新日期:2004-01-01 00:00:00

  • Activated immune system and inflammation in healthy ageing: relevance for tryptophan and neopterin metabolism.

    abstract::Immune activation not only accompanies inflammation in various disorders including infections, autoimmune syndromes and cancer, but it also represents a characteristic feature of ageing. Immune deviations which are most widely expressed in the elderly include increased neopterin production and tryptophan breakdown. Th...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612820666140317110217

    authors: Capuron L,Geisler S,Kurz K,Leblhuber F,Sperner-Unterweger B,Fuchs D

    更新日期:2014-01-01 00:00:00

  • The Impact of Small Heat Shock Proteins (HspBs) in Alzheimer's and Other Neurological Diseases.

    abstract:BACKGROUND:Heat shock proteins are powerful endogenous cytoprotective proteins which help cells to survive recurrent cellular stress events. Identifying the underlying molecular mechanisms and molecular targets is especially interesting since it may help to develop new therapeutic strategies for the treatment of diseas...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666160519113339

    authors: Golenhofen N,Bartelt-Kirbach B

    更新日期:2016-01-01 00:00:00

  • Plasma Non-cholesterol Sterols as Markers of Cholesterol Synthesis and Intestinal Absorption: A Critical Review.

    abstract::Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666200730220230

    authors: Quintão ECR

    更新日期:2020-01-01 00:00:00

  • Ocular involvement in fetal alcohol spectrum disorder: a review.

    abstract::Fetal Alcohol Syndrome (FAS), the most severe manifestation of Fetal Alcohol Spectrum Disorder (FASD) is considered the leading non-hereditary cause of mental retardation and neurological deficit in the Western world. There lie a huge associated human cost to both FASD victims and their families and a considerable fin...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612820666140205144114

    authors: Brennan D,Giles S

    更新日期:2014-01-01 00:00:00

  • Effect of Capsinoids Supplementation on Fat Oxidation and Muscle Glycogen Restoration During Post-exercise Recovery in Humans.

    abstract:Background:Capsinoids (CSN), the novel non-pungent capsaicin analogs have been reported to promote metabolic health and exercise tolerance. However, the effect of CSN on fat oxidation and changes in skeletal muscle glycogen levels during post-exercise recovery has not been investigated in humans. Purpose:We examined t...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666200824104856

    authors: Liao SF,Korivi M,Tsao JP,Huang CC,Chang CC,Cheng IS

    更新日期:2020-08-23 00:00:00

  • Angiotensin II type 1 and type 2 receptor-induced cell signaling.

    abstract::The octapeptide angiotensin II (Ang II) plays a homeostatic role in the regulation of blood pressure and water and electrolyte balance, and also contributes to the progression of cardiovascular remodeling. Ang II activates Ang II type 1 (AT1) receptor and type 2 (AT2) receptor, both of which belong to the seven-transm...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811319170003

    authors: Akazawa H,Yano M,Yabumoto C,Kudo-Sakamoto Y,Komuro I

    更新日期:2013-01-01 00:00:00

  • Synergistic antiproliferative and antiangiogenic effects of EGFR and mTOR inhibitors.

    abstract::Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in ca...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:

    authors: Porcelli L,Quatrale AE,Mantuano P,Silvestris N,Rolland JF,Biancolillo L,Paradiso A,Azzariti A

    更新日期:2013-01-01 00:00:00

  • Implications of the molecular basis of prostacyclin biosynthesis and signaling in pharmaceutical designs.

    abstract::Prostacyclin (PGI(2)) is one of the major vascular protectors against thrombosis and vasoconstriction, caused by thromboxane A(2). Understanding the molecular mechanisms of PGI(2) biosynthesis and signaling is crucial to the development of therapeutic approaches to regulate PGI(2) functions. This review provides infor...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206776055994

    authors: Ruan KH,Dogné JM

    更新日期:2006-01-01 00:00:00

  • Bioprospecting of Nitrogenous Heterocyclic Scaffolds with Potential Action for Neglected Parasitosis: A Review.

    abstract::Neglected parasitic diseases are a group of infections currently considered as a worldwide concern. This fact can be attributed to the migration of these diseases to developed and developing countries, associated with therapeutic insufficiency resulted from the low investment in the research and development of new dru...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612826666200701160904

    authors: Albino SL,da Silva JM,de C Nobre MS,de M E Silva YMS,Santos MB,de Araújo RSA,do C A de Lima M,Schmitt M,de Moura RO

    更新日期:2020-01-01 00:00:00