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
  • Therapeutic effects of micronutrient supplements on sperm parameters: Fact or Fiction?

    abstract:BACKGROUND:Despite the limited evidence about the effect of micronutrient supplementation on the semen quality, many micronutrient supplements have been used to improve male fertility. Approximately, 40%-50% of male infertility cases in general and up to 80% in men with idiopathic infertility cases are caused by oxidat...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666200415173537

    authors: Dimitriadis F,Tsounapi P,Zachariou A,Kaltsas A,Sokolakis I,Hatzichristodoulou G,Symeonidis EN,Kotsiris D,Gabales MR,Vlachopoulou E,Takenaka A,Sofikitis N

    更新日期:2020-04-15 00:00:00

  • Genomics can advance the potential for probiotic cultures to improve liver and overall health.

    abstract::The concept of probiotics has evolved immensely since it was first proposed a century ago. There are numerous potential health benefits attributed to certain probiotic bacteria, from preventing gastrointestinal (GI) infections to stimulating the immune system. Recent evidence is now quite compelling for a role of prob...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161208784480234

    authors: O'Sullivan DJ

    更新日期:2008-01-01 00:00:00

  • Drugs acting on DNA topoisomerases: recent advances and future perspectives.

    abstract::DNA-topoisomerases, a family of DNA-processing enzymes, represent the pharmacological target of major clinically useful chemotherapeutic agents. These drugs essentially act by trapping a topoisomerase-DNA cleavable complex, an intermediate in the enzyme s catalytic cycle. Research activity in this field continues to g...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:

    authors: Gatto B,Capranico G,Palumbo M

    更新日期:1999-03-01 00:00:00

  • A point of view: The need to identify an antigen in psyconeuroimmunological disorders.

    abstract::Several lines of evidence support a mutual relationship between the nervous system and the immune system. Therefore, it is not surprising that some neuropsychiatric disorders are also characterized by immune abnormalities. In patients with phobic disorders and in patients with migraine without aura some common immune ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612033454234

    authors: Covelli V,Pellegrino NM,Jirillo E

    更新日期:2003-01-01 00:00:00

  • Adipose Tissue Oxygenation in Obesity: A Matter of Cardiovascular Risk?

    abstract::Obesity, a chronic low-grade inflammation disorder characterized by an expansion in adipose tissue mass, is rapidly expanding worldwide leading to an increase in the incidence of comorbidities such as insulin resistance, type 2 diabetes and cardiovascular diseases. This has led to a renewed interest in the adipose tis...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666151109111958

    authors: Landini L,Honka MJ,Ferrannini E,Nuutila P

    更新日期:2016-01-01 00:00:00

  • Ligand Conjugated Targeted Nanotherapeutics for Treatment of Neurological Disorders.

    abstract:BACKGROUND:Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612826666200417141600

    authors: Mittal S,Ashhar MU,Qizilbash FF,Qamar Z,Narang JK,Kumar S,Ali J,Baboota S

    更新日期:2020-01-01 00:00:00

  • Essential Oil and Ethanol Extract of Oregano (Origanum vulgare L.) from Armenian Flora as a Natural Source of Terpenes, Flavonoids and other Phytochemicals with Antiradical, Antioxidant, Metal Chelating, Tyrosinase Inhibitory and Antibacterial Activity.

    abstract:BACKGROUND:Origanum vulgare is used in Armenian cuisine as well as in folk medicine. The aim of this investigation was to determine the peculiarities of the chemical composition of Armenian flora's oregano essential oil (EO) and ethanol extract (EE) and to characterize mainly antioxidant and antibacterial properties in...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612825666190702095612

    authors: Moghrovyan A,Sahakyan N,Babayan A,Chichoyan N,Petrosyan M,Trchounian A

    更新日期:2019-01-01 00:00:00

  • Toll-like receptors in human infectious diseases.

    abstract::Toll-like receptors (TLRs) have emerged as critical players in immunity. They are capable of sensing organisms ranging from protozoa to bacteria, fungi or viruses upon detection of the pathogen as well as recognizing endogenous ligands, and triggering transduction pathways. Following activation of the innate immune sy...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206778743493

    authors: de la Barrera S,Alemán M,Sasiain Mdel C

    更新日期:2006-01-01 00:00:00

  • Inflammation, infection and preterm birth.

    abstract::Preterm birth is the leading cause of perinatal morbidity and mortality. Pathological processes that have been linked with preterm birth infection and / or intrauterine inflammation are most frequently found associated with their induction. Studies in animal models and human research showed prior infections to the ind...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612820666140130202224

    authors: Burdet J,Rubio AP,Salazar AI,Ribeiro ML,Ibarra C,Franchi AM

    更新日期:2014-01-01 00:00:00

  • Medical management of the diabetic patient with coronary artery disease.

    abstract::The prevalence of type 2 diabetes is rising at an alarming rate worldwide. Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the diabetic population. Future CAD risk should be routinely assessed in patients with diabetes as specific subgroups might benefit from information derived from c...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161208786071272

    authors: Karastergiou K,Kaski JC

    更新日期:2008-01-01 00:00:00

  • Disorder-specific emotional imagery for differential and quantitative assessment of agoraphobia.

    abstract::Visual emotional stimulation is supposed to elicit psycho-vegetative reactions, which are similar to as the ones elicited by exposure to actual experience. Visual stimulation paradigms have been widely used in studies on agoraphobia with and without panic disorder. However, the applied imagery has hardly ever been dis...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/138161212803530862

    authors: Engel KR,Bandelow B,Neumann C,Obst K,Wedekind D

    更新日期:2012-01-01 00:00:00

  • An Updated Review of Disulfiram: Molecular Targets and Strategies for Cancer Treatment.

    abstract::Repurposing already approved drugs as new anticancer agents is a promising strategy considering the advantages such as low costs, low risks and less time-consumption. Disulfiram (DSF), as the first drug for antialcoholism, was approved by the U.S. Food and Drug Administration (FDA) over 60 years ago. Increasing eviden...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612825666190816233755

    authors: Yang Q,Yao Y,Li K,Jiao L,Zhu J,Ni C,Li M,Dou QP,Yang H

    更新日期:2019-01-01 00:00:00

  • Cellular receptors of extracellular matrix molecules.

    abstract::Extracellular matrix (ECM) is composed of large collagen fibrils. Glycoproteins, such as fibronectin, can bind to collagen or form their own networks. Collagen fibrils are also decorated by proteoglycans, proteins that have large glycosaminoglycan sidechains. In addition, extracellular space often contains hyaluronan,...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161209787846720

    authors: Heino J,Käpylä J

    更新日期:2009-01-01 00:00:00

  • Angiotensin (1-7) and other angiotensin peptides.

    abstract::In the classical renin angiotensin system (RAS), angiotensin II Ang IIplays many important roles in cardiovascular disease and in kidney, brain, and other organs via the Ang II type 1 receptor (AT1). The RAS consists of many angiotensin peptides, including Ang (1-7), Ang (1-9), Ang (2-8), and Ang IV. Ang (1-7), produc...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811319170013

    authors: Ohishi M,Yamamoto K,Rakugi H

    更新日期:2013-01-01 00:00:00

  • Genetic and epigenetic regulation of phosphoinositide 3-kinase isoforms.

    abstract::The last quarter of a century has witnessed remarkable progress in the understanding of phosphoinositide 3-kinases (PI3K) signalling and their involvement in different diseases such as cancer, diabetes and inflammation. Nevertheless, many questions remain open and among these the role of genetic and epigenetic regulat...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:

    authors: Fyffe C,Buus R,Falasca M

    更新日期:2013-01-01 00:00:00

  • Novel targets for antiinflammatory and antiarthritic agents.

    abstract::Inflammation is a complex pathological condition associated with exaggerated human immune system involving various activated immune cells and bio-molecules. Treatment of inflammatory diseases particularly chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease etc. has been a big challen...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206777698945

    authors: Kulkarni RG,Achaiah G,Sastry GN

    更新日期:2006-01-01 00:00:00

  • Radiopharmaceuticals for oncology drug development: a pharmaceutical industry perspective.

    abstract::Oncology remains an increasingly important focus of therapeutic development yet there remain many scientific and operational bottlenecks to deliver optimum treatments efficiently. Radiopharmaceuticals constitute a group of methodologies able to support the many stages of drug development. Methods such as [(18)F]-FDG-P...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161209787581977

    authors: Murphy PS,Bergström M

    更新日期:2009-01-01 00:00:00

  • Current therapeutic strategies and future perspectives for the prevention of arterial thromboembolism: focus on atrial fibrillation.

    abstract::Arterial thromboembolism is a sudden obstruction of arterial blood flow caused by dislodgment of a blood clot from the site of its formation. Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major risk factor for arterial thromboembolism in clinical practice. Most of AF-related arterial thromboembo...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210793563400

    authors: Potpara TS,Lip GY

    更新日期:2010-01-01 00:00:00

  • Vitamin D: A Micronutrient Regulating Genes.

    abstract:BACKGROUND:At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the tra...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612825666190705193227

    authors: Carlberg C

    更新日期:2019-01-01 00:00:00

  • DNA Methylation: An Epigenetic Insight into Type 2 Diabetes Mellitus.

    abstract::DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mell...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612822666160527111152

    authors: Alam F,Islam MA,Gan SH,Mohamed M,Sasongko TH

    更新日期:2016-01-01 00:00:00

  • P2Y purinoceptors as potential emerging therapeutical target in vascular disease.

    abstract::In the last two decades a tremendous development has been noticed in our understanding of the purinergic system, consisting of heterogeneously expressed purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate, uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert mult...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161212803582504

    authors: Schuchardt M,Tölle M,van der Giet M

    更新日期:2012-01-01 00:00:00

  • Is time to change to halogenated drugs in cardiac surgery, what do we have to do with propofol?

    abstract::There is initial evidence, at least in cardiac surgery, that total intra-venous anesthesia (usually a propofol-based total intravenous anesthesia) is associated with an increased mortality when compared to an anesthetic plan including a halogenated anesthetics. The cardiac protective properties of halogenated agents (...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1570161112666140123105536

    authors: Landoni G,Pasin L,Borghi G,Zangrillo A

    更新日期:2014-01-01 00:00:00

  • Exercise as an anabolic stimulus for bone.

    abstract::Mechanical loading provides an anabolic stimulus for bone. More importantly, the mechanosensing apparatus in bone directs osteogenesis to where it is most needed for improving bone strength. The biological processes involved in bone mechanotransduction are poorly understood and further investigation of the molecular m...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612043383755

    authors: Turner CH,Robling AG

    更新日期:2004-01-01 00:00:00

  • Hormones and Sarcopenia.

    abstract::Sarcopenia is defined as the loss of muscle mass associated with a loss of muscle function, e.g., walking speed. A number of consensus definitions exist for sarcopenia with cut-off points being ethnically specific. A rapid screen test (SARC-F) is available and does not require different ethnic cut-off points. Sarcopen...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612823666161123150032

    authors: Morley JE

    更新日期:2017-11-28 00:00:00

  • Alpha2-antiplasmin on cardiovascular diseases.

    abstract::Circumstantial evidence has been provided of a role of the plasminogen/plasmin system in a variety of biological phenomena, including thrombolysis, vascular stenosis, reproduction, embryogenesis, cell invasion, angiogenesis, brain function and chronic lung or kidney inflammatory disorders. Inhibition of the system occ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206776056038

    authors: Matsuno H

    更新日期:2006-01-01 00:00:00

  • Cardiac applications for human pluripotent stem cells.

    abstract::Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can self-renew indefinitely, while maintaining the capacity to differentiate into useful somatic cell types, including cardiomyocytes. As such, these stem cell types represent an essentially inexhaustible source of committed human cardiomyo...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161209788923804

    authors: Shiba Y,Hauch KD,Laflamme MA

    更新日期:2009-01-01 00:00:00

  • Hepatoprotective effects of resveratrol in non-alcoholic fatty live disease.

    abstract:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide directly related to the progressive increase in overweight and obesity. The accumulation of lipids in patients with NAFLD contributes to the development of insulin resistance, inflammatory response a...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666200417165801

    authors: Tejada S,Capó X,Mascaró CM,Monserrat-Mesquida M,Quetglas-Llabrés MM,Pons A,Tur JA,Sureda A

    更新日期:2020-04-17 00:00:00

  • Concept of Hematopoietic and Stromal Niches for Cell-Based Diagnostics and Regenerative Medicine (a Review).

    abstract:BACKGROUND:R. Schofield (1978) proposed a hypothesis of hematopoietic stem cells (HSCs) niche (specialized cell microenvironment). An existence of osteoblastic and vascular niches for HSCs has been postulated since 2003. At the same time, the discussion about the existence and functioning of niche for multipotent mesen...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612824666180829154119

    authors: Khlusov IA,Litvinova LS,Khlusova MY,Yurova KA

    更新日期:2018-01-01 00:00:00

  • Development of a Physiologically-Based Pharmacokinetic Model for Preterm Neonates: Evaluation with In Vivo Data.

    abstract::Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico meth...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612821666150901110533

    authors: Claassen K,Thelen K,Coboeken K,Gaub T,Lippert J,Allegaert K,Willmann S

    更新日期:2015-01-01 00:00:00

  • Gastroduodenal safety of cyclooxygenase-2 inhibitors.

    abstract::Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual C...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612033454018

    authors: Scheiman JM

    更新日期:2003-01-01 00:00:00