Reverse transcriptase inhibitors. Medical search

Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.

A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.

Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.

The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.

The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.

OXAZINES with a fused BENZENE ring.

A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.

Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.

A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1.

Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.

An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49.

Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.

A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.

Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.

The ability of viruses to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutation.

A purine base and a fundamental unit of ADENINE NUCLEOTIDES.

Six-membered heterocycles containing an oxygen and a nitrogen.

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.

Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.

A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.

A type of COUMARINS with added pyran ring(s).

Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)

An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.

A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.

An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.

The phosphate esters of DIDEOXYNUCLEOSIDES.

The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression.

Agents used to treat RETROVIRIDAE INFECTIONS.

Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.

The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.

Therapy with two or more separate preparations given for a combined effect.

Ribonucleic acid that makes up the genetic material of viruses.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series.

The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.

Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.

A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.

A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms as well as RETROVIRUSES.

Inhibitors of HIV INTEGRASE, an enzyme required for integration of viral DNA into cellular DNA.

Defective metabolism leading to fat maldistribution in patients infected with HIV. The etiology appears to be multifactorial and probably involves some combination of infection-induced alterations in metabolism, direct effects of antiretroviral therapy, and patient-related factors.

An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.

The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)

Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE.

The biosynthesis of DNA carried out on a template of RNA.

Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.

A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)

Compounds which inhibit or antagonize biosynthesis or actions of integrase.

The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.

Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.

An HIV species related to HIV-1 but carrying different antigenic components and with differing nucleic acid composition. It shares serologic reactivity and sequence homology with the simian Lentivirus SIMIAN IMMUNODEFICIENCY VIRUS and infects only T4-lymphocytes expressing the CD4 phenotypic marker.

An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.

A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.

A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)

An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.

The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).

Established cell cultures that have the potential to propagate indefinitely.

The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.

Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.

The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.

Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).

Pyridine derivatives with one or more keto groups on the ring.

A species of ALPHARETROVIRUS causing anemia in fowl.

A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.

An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV.

Deoxyribonucleic acid that makes up the genetic material of viruses.

A species of the genus ERYTHROCEBUS, subfamily CERCOPITHECINAE, family CERCOPITHECIDAE. It inhabits the flat open arid country of Africa. It is also known as the patas monkey or the red monkey.

Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.

Inorganic or organic compounds that contain sulfur as an integral part of the molecule.

A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)

Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.

Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).

The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.

Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.

A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.

Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.

Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.

A republic in southern Africa, between NAMIBIA and ZAMBIA. It was formerly called Bechuanaland. Its capital is Gaborone. The Kalahari Desert is in the west and southwest.

The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.

Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.

The rate dynamics in chemical or physical systems.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

Inhibitors of the fusion of HIV to host cells, preventing viral entry. This includes compounds that block attachment of HIV ENVELOPE PROTEIN GP120 to CD4 RECEPTORS.

Elements of limited time intervals, contributing to particular results or situations.

The relationship between the dose of an administered drug and the response of the organism to the drug.

Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.

Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.

Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

A group of compounds that contain the structure SO2NH2.

Keto-pyrans.

The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding.

The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)

The residual portion of BLOOD that is left after removal of BLOOD CELLS by CENTRIFUGATION without prior BLOOD COAGULATION.

Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.

Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.

A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.

Voluntary cooperation of the patient in following a prescribed regimen.

The relationships of groups of organisms as reflected by their genetic makeup.

Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.

Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS do not contain LTRs.

The insertion of drugs into the vagina to treat local infections, neoplasms, or to induce labor. The dosage forms may include medicated pessaries, irrigation fluids, and suppositories.

The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION.

Six-carbon alicyclic hydrocarbons.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

The action of a drug in promoting or enhancing the effectiveness of another drug.

The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.

The presence of viruses in the blood.

The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.

Proteins prepared by recombinant DNA technology.

Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.

Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV).

A transfer RNA which is specific for carrying lysine to sites on the ribosomes in preparation for protein synthesis.

A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.

Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.

DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase.

Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

Simultaneous resistance to several structurally and functionally distinct drugs.

A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.

Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS.

A republic in southern Africa, the southernmost part of Africa. It has three capitals: Pretoria (administrative), Cape Town (legislative), and Bloemfontein (judicial). Officially the Republic of South Africa since 1960, it was called the Union of South Africa 1910-1960.

Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)

A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.

The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.

Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.

A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.

The type species of ALPHARETROVIRUS producing latent or manifest lymphoid leukosis in fowl.

Guanine nucleotides which contain deoxyribose as the sugar moiety.

The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.

Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells. (1/2177)

8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2-methoxyp hen yl)-1- piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12) has recently been identified as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In this study, we examined several combinations of K-12 and other antiretroviral agents for their inhibitory effects on HIV-1 replication in acutely and chronically infected cell cultures. Combinations of K-12 and a reverse transcriptase (RT) inhibitor, either zidovudine, lamivudine, or nevirapine, synergistically inhibited HIV-1 replication in acutely infected MT-4 cells. The combination of K-12 and the protease inhibitor nelfinavir (NFV) also synergistically inhibited HIV-1, whereas the synergism of this combination was weaker than that of the combinations with the RT inhibitors. K-12 did not enhance the cytotoxicities of RT and protease inhibitors. Synergism of the combinations was also observed in acutely infected peripheral blood mononuclear cells. The combination of K-12 and cepharanthine, a nuclear factor kappa B inhibitor, synergistically inhibited HIV-1 production in tumor necrosis factor alpha-stimulated U1 cells, a promonocytic cell line chronically infected with the virus. In contrast, additive inhibition was observed for the combination of K-12 and NFV. These results indicate that the combinations of K-12 and clinically available antiretroviral agents may have potential as chemotherapeutic modalities for the treatment of HIV-1 infection. (+info)

Safety and pharmacokinetics of abacavir (1592U89) following oral administration of escalating single doses in human immunodeficiency virus type 1-infected adults. (2/2177)

Abacavir (1592U89) is a nucleoside analog reverse transcriptase inhibitor that has been demonstrated to have selective activity against human immunodeficiency virus (HIV) in vitro and favorable safety profiles in mice and monkeys. A phase I study was conducted to evaluate the safety and pharmacokinetics of abacavir following oral administration of single escalating doses (100, 300, 600, 900, and 1,200 mg) to HIV-infected adults. In this double-blind, placebo-controlled study, subjects with baseline CD4+ cell counts ranging from < 50 to 713 cells per mm3 (median, 315 cells per mm3) were randomly assigned to receive abacavir (n = 12) or placebo (n = 6). The bioavailability of the caplet formulation relative to that of the oral solution was also assessed with the 300-mg dose. Abacavir was well tolerated by all subjects; mild to moderate asthenia, abdominal pain, headache, diarrhea, and dyspepsia were the most frequently reported adverse events, and these were not dose related. No significant clinical or laboratory abnormalities were observed throughout the study. All doses resulted in mean abacavir concentrations in plasma that exceeded the mean 50% inhibitory concentration (IC50) for clinical HIV isolates in vitro (0.07 microgram/ml) for almost 3 h. Abacavir was rapidly absorbed following oral administration, with the time to the peak concentration in plasma occurring at 1.0 to 1.7 h postdosing. Mean maximum concentrations in plasma (Cmax) and the area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity) increased slightly more than proportionally from 100 to 600 mg (from 0.6 to 4.7 micrograms/ml for Cmax; from 1.0 to 15.7 micrograms.h/ml for AUC0-infinity) but increased proportionally from 600 to 1,200 mg (from 4.7 to 9.6 micrograms/ml for Cmax; from 15.7 to 32.8 micrograms.h/ml for AUC0-infinity. The elimination of abacavir from plasma was rapid, with an apparent elimination half-life of 0.9 to 1.7 h. Abacavir was well absorbed, with a relative bioavailability of the caplet formulation of 96% versus that of an oral solution (drug substance in water). In conclusion, this study showed that abacavir is safe and is well tolerated by HIV-infected subjects and demonstrated predictable pharmacokinetic characteristics when it was administered as single oral doses ranging from 100 to 1,200 mg. (+info)

Safety and single-dose pharmacokinetics of abacavir (1592U89) in human immunodeficiency virus type 1-infected children. (3/2177)

Abacavir (formerly 1592U89) is a potent 2'-deoxyguanosine analog reverse transcriptase inhibitor that has been demonstrated to have a favorable safety profile in initial clinical trials with adults with human immunodeficiency virus (HIV) type 1 infection. A phase I study was conducted to evaluate the pharmacokinetics and safety of abacavir following the administration of two single oral doses (4 and 8 mg/kg of body weight) to 22 HIV-infected children ages 3 months to 13 years. Plasma was collected for analysis at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, and 8 h after the administration of each dose. Plasma abacavir concentrations were determined by high-performance liquid chromatography, and data were analyzed by noncompartmental methods. Abacavir was well tolerated by all subjects. The single abacavir-related adverse event was rash, which occurred in 2 of 22 subjects. After administration of the oral solution, abacavir was rapidly absorbed, with the time to the peak concentration in plasma occurring within 1.5 h postdosing. Pharmacokinetic parameter estimates were comparable among the different age groups for each dose level. The mean maximum concentration in plasma (Cmax) and the mean area under the curve from time zero to infinity (AUC0-infinity) increased by 16 and 45% more than predicted, respectively, as the abacavir dose was doubled from 4 to 8 mg/kg (Cmax increased from 1.69 to 3.94 micrograms/ml, and AUC0-infinity increased from 2.82 to 8.09 micrograms.h/ml). Abacavir was rapidly eliminated, with a mean elimination half-life of 0.98 to 1.13 h. The mean apparent clearance from plasma decreased from 27.35 to 18.88 ml/min/kg as the dose increased. Neither body surface area nor creatinine clearance were correlated with pharmacokinetic estimates at either dose. The extent of exposure to abacavir appears to be slightly lower in children than in adults, with the comparable unit doses being based on body weight. In conclusion, this study showed that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg. (+info)

Suppression of replication of multidrug-resistant HIV type 1 variants by combinations of thymidylate synthase inhibitors with zidovudine or stavudine. (4/2177)

The replication of recombinant multidrug-resistant HIV-1 clones modeled on clinically derived resistant HIV-1 strains from patients receiving long-term combination therapy with zidovudine (AZT) plus 2',3'-dideoxycytidine was found to regain sensitivity to AZT and stavudine (D4T) as a consequence of a pharmacologically induced decrease in de novo dTMP synthesis. The host-cell system used was phytohemagglutinin-stimulated peripheral blood mononuclear cells; dTMP and dTTP depletion were induced by single exposures to a low level of the thymidylate synthase inhibitor 5-fluorouracil (5-FU) or its deoxynucleoside, 2'-deoxy-5-fluorouridine. The host-cell response to the latter was biphasic: a very rapid decrease in the rate of de novo dTMP formation and, consequently, in intracellular dTTP pools, followed by slower recovery in both indices over 3 to 24 h. With the additional presence of AZT or D4T, however, replication of the multidrug-resistant HIV-1 strains remained inhibited, indicating dependence of HIV DNA chain termination by AZT-5'-monophosphate or 2',3'-didehydro-2', 3'-dideoxythymidine-5'-monophosphate in these resistant strains on simultaneous inhibition of host-cell de novo synthesis of thymidine nucleotides. No effect on viability of control (uninfected) phytohemagglutinin-stimulated/peripheral blood mononuclear cells was noted on 6-day exposures to 5-FU or 2'-deoxy-5-fluorouridine alone or in combination with AZT or D4T, even at drug levels severalfold higher than those used in the viral inhibition studies. These studies may provide useful information for the potential clinical use of AZT/5-FU or D4T/5-FU combinations for the prevention or reversal of multidrug resistance associated with long-term dideoxynucleoside combination therapy. (+info)

Functional analysis of mutations conferring lamivudine resistance on hepatitis B virus. (5/2177)

Two patterns of mutation are commonly observed in the polymerase gene of lamivudine [(-)2'-deoxy-3'-thiacytidine]-resistant hepatitis B virus (HBV). The M539I substitution in the conserved YMDD motif occurs independently of other changes, whereas the M539V substitution is associated with an additional upstream change (L515M). These mutations were introduced into a common background and their effects on HBV DNA replication and lamivudine resistance studied. The L515M and M539V mutations provided only partial resistance while the M539I mutation conferred a high degree of lamivudine resistance. The combination of the L515M and M539V mutations gave an intermediate level of replication competence, compared with either mutation alone, and increased resistance to lamivudine. This probably accounts for these two mutations always being observed together. The M539I mutation reduced replication competence. (+info)

The cost-effectiveness of treatment with lamivudine and zidovudine compared with zidovudine alone: a comparison of Markov model and trial data estimates. (6/2177)

In this paper, we present a Markov model for estimating the cost-effectiveness of combination therapy with lamivudine (LMV) and zidovudine (ZDV) compared with ZDV alone. We also compare the predictions of the Markov model for the impact of combination therapy on trial period costs with the actual impact of combination therapy on selected trial period costs estimated from data collected during the clinical trials. In the Markov model, disease stages were defined by CD4 cell count. Based on clinical trial data for patients with CD4 counts higher than 100 cells/mm3, the model assumed that the CD4 cell count level could be maintained above the level at the initiation of therapy for 6.5 months with monotherapy and for 18 months with combination therapy. After this period, transition rates for natural disease progression were used. Incremental lifetime costs and quality-adjusted life years gained with LMV/ZDV compared with ZDV alone were estimated for cohorts of patients initiating antiretroviral therapy at four different CD4 cell count stages. Cost per life year gained varied from $10,000 to $18,000, and cost per quality-adjusted life year gained varied from $14,000 to $27,000. In both cases, the combination therapy was more cost-effective when started earlier in disease progression. These estimates were not sensitive to changes in key parameter values. In addition, the model was used to estimate the impact of combination therapy on healthcare costs during the trial period; these estimated costs were compared with data on the cost of resource use collected during the clinical trial for hospital stays, unscheduled visits, medications, and outpatient procedures. Both the Markov model estimates and the trial data estimates for the trial period showed cost savings in other medical costs, though these were not large enough to completely offset the increased cost for antiretroviral therapy. The model estimates were more conservative than the estimates based on the trial data. (+info)

Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. (7/2177)

Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were +info)

Genotypic resistance and the treatment of HIV-1 infection in Espirito Santo, Brazil. (8/2177)

Before December 1997, in Espirito Santo, Brazil, combination antiretroviral therapy was used without routine virologic or immunologic monitoring. To examine consequences of therapy in this setting, clinical information, human immunodeficiency virus type 1 (HIV-1) RNA levels, CD4 cell counts, and protease and reverse transcriptase sequences were determined for consecutive HIV-1-infected outpatients. Of 48 treatment-naive individuals, 11 were started on therapy for HIV-related symptoms; however, 44 (92%) had an RNA level >20,000 copies/mL, a CD4 cell count <500/mm3, or symptoms. Eighteen (51%) of 35 patients on therapy had an RNA level >20,000 copies/mL. Nucleoside-resistance mutations were observed in 21 (68%) of 31 nucleoside-experienced subjects. Protease mutations necessary for high-level protease inhibitor (PI) resistance were present together with permissive mutations in 3 of 10 PI-experienced patients. Inability to identify high-risk individuals and to detect virologic failure may limit the effectiveness of antiretroviral drug programs and may promote the spread of drug resistance where virologic and immunologic monitoring are not available. (+info)

Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs) Non-nucleoside reverse-transcriptase inhibitors (NNRTIs ... Discovery and development of non-nucleoside reverse-transcriptase inhibitors Protease inhibitors Discovery and development of ... Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some ... Reverse+Transcriptase+Inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH) (Articles with short ...

https://en.wikipedia.org/wiki/Reverse-transcriptase_inhibitor

... nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs/NtRTIs) and non-nucleoside reverse-transcriptase inhibitors ( ... Medicine portal Viruses portal Antiretroviral drug Reverse-transcriptase inhibitor Protease inhibitor Entry inhibitor Discovery ... Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are antiretroviral drugs used in the treatment of human ... Jochmans D (June 2008). "Novel HIV-1 reverse transcriptase inhibitors". Virus Research. 134 (1-2): 171-85. doi:10.1016/j. ...

https://en.wikipedia.org/wiki/Discovery_and_development_of_non-nucleoside_reverse-transcriptase_inhibitors

... protease inhibitors, entry inhibitors, co-receptor inhibitors and integrase inhibitors. The reverse transcriptase of HIV-1 has ... Nucleoside and nucleotide reverse-transcriptase inhibitors, Non-nucleoside reverse-transcriptase inhibitors, ... development of CCR5 receptor antagonists HIV/AIDS research Reverse-transcriptase inhibitor Protease inhibitor Entry inhibitor ... non-nucleoside reverse-transcriptase inhibitors and protease inhibitors. Currently, there are several NRTIs in various stages ...

https://en.wikipedia.org/wiki/Discovery_and_development_of_nucleoside_and_nucleotide_reverse-transcriptase_inhibitors

Bumpus has also researched nonnucleoside reverse transcriptase inhibitors. Her lab was the first to publish the P450-catalyzed ... Nucleotide Reverse Transcriptase Inhibitors". Expert Opinion on Pharmacotherapy. 13 (1): 65-79. doi:10.1517/14656566.2012. ... Tenofovir is a nucleotide analog reverse transcriptase inhibitor that prevents the HIV virus from replicating. Tenofovir is ... rilpivirine and etravirine and was first to characterize the metabolism of the nonnucleoside reverse transcriptase inhibitor ...

https://en.wikipedia.org/wiki/Namandjé_Bumpus

Montessori V, Harris M, Montaner JS (2003). "Hepatotoxicity of nucleoside reverse transcriptase inhibitors". Seminars in Liver ... including nucleoside reverse transcriptase inhibitors used to treat HIV, and a rare condition known as Jamaican vomiting ...

https://en.wikipedia.org/wiki/Acute_fatty_liver_of_pregnancy

... such as a protease inhibitor, non-nucleoside reverse-transcriptase inhibitor, or integrase inhibitor; this type of therapy is ... ZDV is of the nucleoside analog reverse-transcriptase inhibitor (NRTI) class. It works by inhibiting the enzyme reverse ... Their research efforts were focused in part on the viral enzyme reverse transcriptase. Reverse transcriptase is an enzyme that ... Quan, Y; Rong, L; Liang, C; Wainberg, MA (1999). "Reverse Transcriptase Inhibitors Can Selectively Block the Synthesis of ...

https://en.wikipedia.org/wiki/Zidovudine

Olivero, Ofelia A. (April 2007). "Mechanisms of genotoxicity of nucleoside reverse transcriptase inhibitors". Environmental and ...

https://en.wikipedia.org/wiki/Ofelia_Olivero

It is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Elsulfavirine is a prodrug which is metabolized to the active ... Wang Y, De Clercq E, Li G (October 2019). "Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for ... Wang Y, De Clercq E, Li G (October 2019). "Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for ... Rai MA, Pannek S, Fichtenbaum CJ (June 2018). "Emerging reverse transcriptase inhibitors for HIV-1 infection". Expert Opinion ...

https://en.wikipedia.org/wiki/Elsulfavirine

... reverse-transcriptase inhibitors targeting HIV/AIDS, neuraminidase inhibitors targeting influenza, and terminase inhibitors ... Li G, Wang Y, De Clercq E (April 2022). "Approved HIV reverse transcriptase inhibitors in the past decade". Acta Pharmaceutica ... For example, an inhibitor might compete with substrate A for the first binding site, but be a non-competitive inhibitor with ... New inhibitors are used to obtain crystallographic structures of the enzyme in an inhibitor/enzyme complex to show how the ...

https://en.wikipedia.org/wiki/Enzyme_inhibitor

"Nucleoside reverse transcriptase inhibitors (NRTIs or 'nukes') - HIV/AIDS". www.hiv.va.gov. Archived from the original on 9 ... Abacavir is a nucleoside reverse transcriptase inhibitor that inhibits viral replication. It is a guanosine analogue that is ... Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV ... a Potent Inhibitor of HIV Reverse Transcriptase". The Journal of Organic Chemistry. 61 (13): 4192-4193. doi:10.1021/jo960708p. ...

https://en.wikipedia.org/wiki/Abacavir

v t e (Reverse transcriptase inhibitors, Antiretroviral drugs, Integrase inhibitors, All stub articles, Antiinfective agent ... Minnesota researchers who designed and synthesized a combination HIV reverse transcriptase inhibitor and an integrase inhibitor ... "Rationally Designed Dual Inhibitors of HIV Reverse Transcriptase and Integrase". Journal of Medicinal Chemistry. 50 (15): 3416- ... A portmanteau inhibitor is a drug that is a combination of two drug molecules, each of which is itself a type of inhibitor. The ...

https://en.wikipedia.org/wiki/Portmanteau_inhibitor

It belongs to the class of nucleoside reverse transcriptase inhibitors.[citation needed] KP-1461 is a prodrug of the active ... Reverse transcriptase inhibitors, Experimental drugs, Prodrugs, All stub articles, Antiinfective agent stubs). ...

https://en.wikipedia.org/wiki/KP-1461

"Interface Peptides as Structure-based Human Immunodeficiency Virus Reverse Transcriptase Inhibitors". Journal of Biological ... Rittinger, K; Divita, G; Goody, R S (1995-08-15). "Human immunodeficiency virus reverse transcriptase substrate-induced ... Rittinger studied human immunodeficiency virus reverse transcriptase. At MRC National Institute for Medical Research Rittinger ... She has also collaborated with GlaxoSmithKline to discover inhibitors targeting the active site cysteine of thioester-forming ...

https://en.wikipedia.org/wiki/Katrin_Rittinger

It is of the reverse-transcriptase inhibitor class. Didanosine was first described in 1975 and approved for use in the United ... Nucleoside analog reverse transcriptase inhibitors, Purines, Hepatotoxins, Bristol Myers Squibb, Hydroxymethyl compounds). ... Like other anti-HIV nucleoside analogs, it acts as a chain terminator by incorporation and inhibits viral reverse transcriptase ...

https://en.wikipedia.org/wiki/Didanosine

It is a non-nucleoside reverse transcriptase inhibitor. While emivirine showed promising antiviral activity in vitro, it failed ... Non-nucleoside reverse transcriptase inhibitors, Pyrimidinediones, Isopropyl compounds, Benzyl compounds, All stub articles, ...

https://en.wikipedia.org/wiki/Emivirine

Then, add an RNase inhibitor and reverse transcriptase to the PCR tube. Next, place the PCR tube into a thermal cycler for one ... Once a one-step RT-PCR kit with a mix of reverse transcriptase, Taq DNA polymerase, and a proofreading polymerase is selected ... September 2002). "Development of a real-time reverse transcriptase PCR assay for type A influenza virus and the avian H5 and H7 ... The two-step reaction requires that the reverse transcriptase reaction and PCR amplification be performed in separate tubes. ...

https://en.wikipedia.org/wiki/Reverse_transcription_polymerase_chain_reaction

Menéndez-Arias L (June 2008). "Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase". ...

https://en.wikipedia.org/wiki/Nucleoside_triphosphate

Trachtenberg, Joel D; Sande Merle A (July 2002). "Emerging resistance to nonnucleoside reverse transcriptase inhibitors: a ...

https://en.wikipedia.org/wiki/Merle_Sande

... is in the nucleoside reverse transcriptase inhibitors (NRTIs) family of medications. It prevents the hepatitis B ... Nucleoside analog reverse transcriptase inhibitors, Purines, Hepatotoxins, World Health Organization essential medicines, ... virus from multiplying by blocking reverse transcriptase. Entecavir was approved for medical use in 2005. It is on the World ... proven more selective potent inhibitor of HBV by virtue of being Guanine NA 1998: Inhibition of hepadnaviral polymerases was ...

https://en.wikipedia.org/wiki/Entecavir

Ateviridine is a non-nucleoside reverse transcriptase inhibitor that has been studied for the treatment of HIV. Preparation of ... 1. A Novel Class of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors". Journal of Medicinal Chemistry. 37 (7): 999-1014. ... Non-nucleoside reverse transcriptase inhibitors, Piperazines, Aminopyridines, All stub articles, Antiinfective agent stubs). ... amine with the imidazolide derivative of 5-methoxy-3-indoleacetic acid produces the amide reverse transcriptase inhibitor, ...

https://en.wikipedia.org/wiki/Atevirdine

It acts as a nucleoside reverse transcriptase inhibitor (NRTI). The drug was discovered by Raymond F. Schinazi (Emory ... Nucleoside analog reverse transcriptase inhibitors, Purines, Dioxolanes, Experimental drugs, Hydroxymethyl compounds, All stub ...

https://en.wikipedia.org/wiki/Amdoxovir

... is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, ... Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV ... who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) ... and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug- ...

https://en.wikipedia.org/wiki/Etravirine

Nucleotide reverse transcriptase inhibitor, Treatment of HIV-1 infection". Drugs of the Future. 45 (7): 459. doi:10.1358/DOF. ... Rovafovir etalafenamide is a nucleotide reverse transcriptase inhibitor and prodrug of GS-9148. Rovafovir etalafenamide itself ... Reverse transcriptase inhibitors, Experimental drugs, Purines, Dihydrofurans, Ethyl esters, Phosphonate esters, All stub ... against viruses containing major mutations associated with resistance to the nucleoside analog reverse-transcriptase inhibitors ...

https://en.wikipedia.org/wiki/Rovafovir_etalafenamide

It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and ... Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). When taken by mouth, rilpivirine reaches highest ... Lade JM, Avery LB, Bumpus NN (October 2013). "Human biotransformation of the nonnucleoside reverse transcriptase inhibitor ... Non-nucleoside reverse transcriptase inhibitors, Nitriles, Pyrimidines, Johnson & Johnson brands). ...

https://en.wikipedia.org/wiki/Rilpivirine

... a reverse-transcriptase inhibitor used for HIV; cepharanthine, an alkaloid from stephania cepharantha hayata; and phosphonated ... "Susceptibility of Primary HTLV-1 Isolates from Patients with HTLV-1-Associated Myelopathy to Reverse Transcriptase Inhibitors ... HTLV-1 infection is thought to spread only through dividing cells since reverse transcriptase generates proviral DNA from ...

https://en.wikipedia.org/wiki/Human_T-lymphotropic_virus

... is a nucleotide analog reverse-transcriptase inhibitor (NtRTI). It selectively inhibits viral reverse ... It is a nucleotide reverse transcriptase inhibitor and works by decreasing the ability of the viruses to replicate. Tenofovir ... Nucleoside analog reverse transcriptase inhibitors, Prodrugs, Purines, World Health Organization essential medicines, Wikipedia ... the active compound that inhibits reverse transcriptase via chain termination. In fasting persons, bioavailability is 25%, and ...

https://en.wikipedia.org/wiki/Tenofovir_disoproxil

HIV-1 reverse transcriptase complexed with different inhibitors, by Temiz and Bahar, 2002. - HIV-1 protease, by Micheletti et ... application to alpha-amylase inhibitor", Doruker, P, Atilgan, AR & Bahar, I, Proteins, 15, 512-524, (2000). Hinsen, K. (1998) " ...

https://en.wikipedia.org/wiki/Anisotropic_Network_Model

Non-nucleoside reverse-transcriptase inhibitors have been shown to both induce and inhibit CYP3A4. Hidaka M, Fujita K, Ogikubo ... Inhibitors of CYP3A4 can be classified by their potency, such as: Strong inhibitor being one that causes at least a 5-fold ... Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% ... Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance. ...

https://en.wikipedia.org/wiki/CYP3A4

Other applications include the discovery of new Myeloperoxidase ligands, HIV reverse transcriptase inhibitors, applications in ... "Structure-Based Pharmacophore Identification of New Chemical Scaffolds as Non-Nucleoside Reverse Transcriptase Inhibitors". J. ... "Structure-Based Pharmacophore Identification of New Chemical Scaffolds as Non-Nucleoside Reverse Transcriptase Inhibitors". ... 3-dicarboxylic acid inhibitors of bacterial MurD and MurE ligases by structure-based virtual screening approach". Bioorganic & ...

https://en.wikipedia.org/wiki/Inte:Ligand

Some notable drugs containing trifluoromethyl groups include efavirenz (Sustiva), an HIV reverse transcriptase inhibitor; ...

https://en.wikipedia.org/wiki/Trifluoromethyl_group

Cozaar Losartan angiotensin II receptor antagonist to treat hypertension Sustiva Efavirenz reverse transcriptase inhibitor for ...

https://en.wikipedia.org/wiki/List_of_DuPont_Experimental_Station_inventions

Reverse transcriptase - RFLP - rho factor - rhodopsin - ribonucleoprotein - ribose - ribosomal protein - ribosomal protein S6 ... inhibitor - inhibitory gi G-protein - Inorganic chemistry - insect protein - Insulin - insulin receptor - insulin-like growth ...

https://en.wikipedia.org/wiki/Index_of_biochemistry_articles

TERT is a reverse transcriptase, which is a class of enzymes that creates single-stranded DNA using single-stranded RNA as a ... small-molecule and signal pathway inhibitors. The ability to maintain functional telomeres may be one mechanism that allows ... Telomerase is a reverse transcriptase enzyme that carries its own RNA molecule (e.g., with the sequence 3′-CCCAAUCCC-5′ in ... Vulliamy TJ, Walne A, Baskaradas A, Mason PJ, Marrone A, Dokal I (2005). "Mutations in the reverse transcriptase component of ...

https://en.wikipedia.org/wiki/Telomerase

In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus ...

https://en.wikipedia.org/wiki/Paul_Lewi

... and biological evaluations of novel oxindoles as HIV-1 non-nucleoside reverse transcriptase inhibitors". Bioorg. Med. Chem. ... Mallamo, J.P. (2006). "Structure-guided identification of novel VEGFR-2 kinase inhibitors via solution phase parallel synthesis ... "Discovery of Tryptanthrin Derivatives as Potent Inhibitors of Indoleamine 2,3-Dioxygenase with Therapeutic Activity in Lewis ...

https://en.wikipedia.org/wiki/Isatin

... with reverse transcriptase activity, and an RNA component, encoded by this gene, that serves as a template for the telomere ... Pruzan R, Pongracz K, Gietzen K, Wallweber G, Gryaznov S (January 2002). "Allosteric inhibitors of telomerase: oligonucleotide ... "Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase ... TERC serves as a template for telomere replication (reverse transcription) by telomerase. Telomerase RNAs differ greatly in ...

https://en.wikipedia.org/wiki/Telomerase_RNA_component

... is a nucleotide reverse-transcriptase inhibitor (NRTI) which interferes with the replication of HIV and is approved in tablet ... a diarylpyrimidine inhibitor of HIV reverse transcriptase) and UC-781. These next-generation microbicides have received ...

https://en.wikipedia.org/wiki/Microbicides_for_sexually_transmitted_diseases

... and when the virus has not developed resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase ... It is an integrase inhibitor with a carbamoyl pyridone structure similar to that of dolutegravir. In December 2021, the U.S. ... Cabotegravir is an integrase strand transfer inhibitor. This means it blocks the HIV's enzyme integrase, thereby preventing its ... Integrase inhibitors, Fluoroarenes, Oxazolidines, 4-Pyridones, Heterocyclic compounds with 3 rings, Carboxamides). ...

https://en.wikipedia.org/wiki/Cabotegravir

Most antiviral drugs against influenza fall into two categories: neuraminidase (NA) inhibitors and M2 inhibitors. Baloxavir ... Among NATs, reverse transcription polymerase chain reaction (RT-PCR) is the most traditional and considered the gold standard ... Three segments encode three subunits of an RNA-dependent RNA polymerase (RdRp) complex: PB1, a transcriptase, PB2, which ... NA inhibitors target the enzymatic activity of NA receptors, mimicking the binding of sialic acid in the active site of NA on ...

https://en.wikipedia.org/wiki/Influenza

Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (May 2007). "Stable complexes formed by HIV-1 reverse transcriptase at ... It is classified as a pyrophosphate analog DNA polymerase inhibitor. Foscarnet is the conjugate base of a chemical compound ... Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (2007). "Stable complexes formed by HIV-1 reverse transcriptase at ... In individuals treated with the DNA polymerase inhibitors acyclovir or ganciclovir, HSV or CMV particles can develop mutant ...

https://en.wikipedia.org/wiki/Foscarnet

... have shown that highly active antiretroviral therapy-regimens including reverse transcriptase and potent protease inhibitors- ... Moreover, damage to the immune system is incompletely reversed. Thus, there is an ongoing, urgent need for new therapeutic ...

https://en.wikipedia.org/wiki/Division_of_Acquired_Immunodeficiency_Syndrome

Mahboubi-Rabbani M, Abbasi M, Hajimahdi Z, Zarghi A (2021). "HIV-1 Reverse Transcriptase/Integrase Dual Inhibitors: A Review of ... The second integrase inhibitor, elvitegravir, was approved in the U.S. in August 2012. Integrase inhibitor Integron Beck BJ, ... Choi E, Mallareddy JR, Lu D, Kolluru S (October 2018). "Recent advances in the discovery of small-molecule inhibitors of HIV-1 ... production of the double-stranded linear viral DNA by the viral RNA/DNA-dependent DNA polymerase reverse transcriptase. The ...

https://en.wikipedia.org/wiki/Integrase

"Telomerase reverse transcriptase delays aging in cancer resistant mice". Cell. 135 (4): 609-622. doi:10.1016/j.cell.2008.09.034 ... which are potent telomerase-inhibitors whose expression is altered in cancer; Demonstration that telomerase activity and ...

https://en.wikipedia.org/wiki/María_Blasco_Marhuenda

... of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block an HIV enzyme called reverse transcriptase ... Elvucitabine is an experimental nucleoside reverse transcriptase inhibitor (NRTI), developed by Achillion Pharmaceuticals, Inc ... Nucleoside analog reverse transcriptase inhibitors, Organofluorides, Pyrimidones, Experimental drugs, Hydroxymethyl compounds, ... An enzyme is a protein that starts or increases the speed of a chemical reaction). By blocking reverse transcriptase, NRTIs ...

https://en.wikipedia.org/wiki/Elvucitabine

He has shown that adherence to non-nucleoside reverse-transcriptase inhibitor HIV therapy has a linear dose-response pattern. ...

https://en.wikipedia.org/wiki/Jean_Nachega

"Quantitative method to determine mRNA levels by reverse transcriptase-polymerase chain reaction from leukocyte subsets purified ... Thus supplementing with CYP 2C9 inhibitors leads to extended intoxication. Some is also stored in fat in addition to being ... Stout SM, Cimino NM (February 2014). "Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing ... cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo". The ...

https://en.wikipedia.org/wiki/Cannabinoid

Reverse Transcription PCR (RT-PCR): for amplifying DNA from RNA. Reverse transcriptase reverse transcribes RNA into cDNA, which ... either by the binding of an antibody or by the presence of covalently bound inhibitors that dissociate only after a high- ... in this test the enzyme reverse transcriptase is used to generate a DNA sequence which matches the viral RNA; this DNA is then ... It is also sometimes abbreviated to RT-PCR (real-time PCR) but this abbreviation should be used only for reverse transcription ...

https://en.wikipedia.org/wiki/Polymerase_chain_reaction

Nucleoside analog reverse transcriptase inhibitors, Pyrimidinediones, Organofluorides, Arabinosides, Halohydrins, Hydroxymethyl ...

https://en.wikipedia.org/wiki/Clevudine

"Reverse transcriptase droplet digital PCR shows high resilience to PCR inhibitors from plant, soil and water samples". Plant ... dPCR is also more resilient to PCR inhibitors for the quantification of RNA than qPCR. dPCR can detect and quantify more ... been used to detect in a single well the expression of four different splice variants of human telomerase reverse transcriptase ... RNA quantification can be accomplished via RT-PCR, wherein RNA is reverse-transcribed into cDNA in the partitioned reaction ...

https://en.wikipedia.org/wiki/Digital_polymerase_chain_reaction

The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity similar to retroviruses. ... Menéndez-Arias L, Álvarez M, Pacheco B (October 2014). "Nucleoside/nucleotide analog inhibitors of hepatitis B virus polymerase ... Hepatitis B is one of a few known non-retroviral viruses which use reverse transcription as a part of its replication process. ... long mRNA is then transported back to the cytoplasm where the virion P protein synthesizes DNA via its reverse transcriptase ...

https://en.wikipedia.org/wiki/Hepatitis_B_virus

... which uses reverse transcriptase as part of its replication process. Researchers have gone further and developed inhibitors ... Improved protease inhibitors are now in development. Protease inhibitors have also been seen in nature. A protease inhibitor ... This approach is more commonly associated with the inhibition of reverse transcriptase (RNA to DNA) than with "normal" ... An improved knowledge of the action of reverse transcriptase has led to better nucleoside analogues to treat HIV infections. ...

https://en.wikipedia.org/wiki/Antiviral_drug

... nucleic acid synthesis inhibitors MeSH D27.505.519.389.675.850 - reverse-transcriptase inhibitors MeSH D27.505.519.389.735 - ... hiv protease inhibitors MeSH D27.505.954.122.388.077.750 - reverse-transcriptase inhibitors MeSH D27.505.954.122.425 - ... enzyme inhibitors MeSH D27.505.519.389.099 - aromatase inhibitors MeSH D27.505.519.389.200 - carbonic anhydrase inhibitors MeSH ... trypsin inhibitors MeSH D27.505.519.389.755 - protein kinase inhibitors MeSH D27.505.519.389.760 - protein synthesis inhibitors ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D27)

The enzyme possesses efficient reverse transcriptase activity in the presence of manganese. This enzyme is beneficial for ... it also has the capacity to detect RNA in the presence of inhibitors. Under the presence of inhibitors, it was shown to detect ... This polymerase has been shown to be resistant to DNA polymerase inhibitors present in clinical samples, ... "Capacity of rTth polymerase to detect RNA in the presence of various inhibitors". PLOS ONE. 13 (1): e0190041. Bibcode:2018PLoSO ...

https://en.wikipedia.org/wiki/Thermus_thermophilus

"Reverse Transcriptase Inhibitors". 0-9. A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P. Q. R. S. T. U. V. W. X. Y. Z. * 0-9 ...

https://extranet.who.int/iris/restricted/browse?authority=Reverse+Transcriptase+Inhibitors&type=mesh

Three-drug combination of a non-nucleoside reverse transcriptase inhibitor, and two nucleo(t)side reverse transcriptase ... Combines integrase strand transfer inhibitor (INSTI) plus nucleoside reverse transcriptase inhibitor (NRTI). ... Antiretroviral agent, nucleoside reverse-transcriptase inhibitor. Class Summary. NRTIs agents inhibit viral replication by ... Antiretroviral agent, non-nucleoside reverse-transcriptase inhibitor. Class Summary. NNRTIs inhibit viral replication. ...

https://www.medscape.com/answers/211316-6887/which-medications-in-the-drug-class-cyp3a4-inhibitors-are-used-in-the-treatment-of-hiv-infection-and-aids

VA » Health Care » HIV » Veterans and Public Home » Treatment » Nucleoside reverse transcriptase inhibitors (NRTIs or nukes) ... It does this by using an enzyme called reverse transcriptase. The NRTIs work because they block that enzyme. Without reverse ...

https://www.hiv.va.gov/patient/treat/NRTIs.asp

companys investigational non-nucleoside reverse transcriptase inhibitor. (NNRTI) for the treatment of HIV-1 infection in ... the Companys Investigational Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), for Treatment of HIV-1 Infection ...

https://www.merck.com/news/fda-accepts-new-drug-applications-for-mercks-doravirine-the-companys-investigational-non-nucleoside-reverse-transcriptase-inhibitor-nnrti-for-treatment-of-hiv-1-infection/

... January 29, 2016 09:00 AM - 10:00 AM ...

http://www.sas.rochester.edu/chm/news-events/events/2016/01/stereoselective-synthesis-of-nucleoside-reverse-transcriptase-inhibitor-nrti-bms-986001.html

This reduction in complexity was most significant for the non-nucleoside reverse transcriptase inhibitor (NNRTI) models, while ... Compared to standard stepwise regression we were able to reduce the number of mutations in the reverse transcriptase (RT) ... inhibitor models as well as the number of interaction terms accounting for synergistic and antagonistic effects. ... From: Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance ...

https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-12-386/tables/4

Level of viral load and antiretroviral resistance after 6 months of non-nucleoside reverse transcriptase inhibitor first-line ... PATIENTS AND METHODS: Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) ... and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were ...

https://research.pasteur.fr/en/publication/level-of-viral-load-and-antiretroviral-resistance-after-6-months-of-non-nucleoside-reverse-transcriptase-inhibitor-first-line-treatment-in-hiv-1-infected-children-in-mali/

... human immunodeficiency virus type 1 reverse transcriptase confer resistance to nonnucleoside reverse transcriptase inhibitors. ... Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel ... A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype a HIV-1 viruses. AIDS ... Phenotypic susceptibility to nonnucleoside inhibitors of Virion-associated reverse transcriptase from different HIV types and ...

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05007-5

From an investigation of lithiation of nucleosides towards a rational design of non-nucleoside reverse transcriptase inhibitors ... From an investigation of lithiation of nucleosides towards a rational design of non-nucleoside reverse transcriptase inhibitors ...

https://www.jenner.ac.uk/publications/95053

Non-nucleoside reverse transcriptase inhibitors. Recommended change in dose of antiretroviral drug ... Ritonavir-boosted protease inhibitors. Recommended change in dose of antiretroviral drug. Recommended change in dose of ...

https://www.cdc.gov/tb/publications/guidelines/tb_hiv_drugs/table2a.htm

HIV reverse transcriptase (RT) is one of the main targets for the action of anti-AIDS drugs. The selection of drug-resistant ... "HIV Reverse Transcriptase Structures: Designing New Inhibitors and Understanding Mechanisms of Drug Resistance." Trends in ... "HIV Reverse Transcriptase Structures: Designing New Inhibitors and Understanding Mechanisms of Drug Resistance." Trends in ... HIV reverse transcriptase structures: designing new inhibitors and understanding mechanisms of drug resistance.. ...

https://ora.ox.ac.uk/objects/uuid:487d76af-e76c-4ca2-8fe8-6115f30e1d44

"Nucleosides Reverse Transcriptase Inhibitors","data":{"category":"Medicine","linkRef":"Nucleosides Reverse Transcriptase ... "Non-nucleosides Reverse Transcriptase Inhibitors","data":{"category":"Medicine","linkRef":"Non-nucleosides Reverse ... ":"ACE Inhibitors"}},{"value":"ACE Inhibitors with Diuretics","data":{"category":"Medicine","linkRef":"ACE Inhibitors with ... Transcriptase Inhibitors"}},{"value":"Non-opioid Analgesics","data":{"category":"Medicine","linkRef":"Non-opioid Analgesics ...

https://schedule.pharmac.govt.nz/ScheduleOnline.php?code=A162003

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT ... HIV reverse transcriptase structure function and role in HIV replication. To study the role of reverse transcriptase ... Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol.. Figueiredo A, Moore KL, Mak J, Sluis-Cremer N, de ... NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the ...

https://burnet.edu.au/publications/1056_potent_nonnucleoside_reverse_transcriptase_inhibitors_target_hiv_1_gag_pol

Synthesis, bioactivity, 3D-QSAR studies of novel HIV-1 reverse transcriptase inhibitors ... Synthesis, bioactivity, 3D-QSAR studies of novel HIV-1 reverse transcriptase inhibitors ... HIV-1 reverse transcriptase inhibitor Category: CYP. Another important concern is that CSF examples cannot be extracted from a ...

https://www.skinmicrobiomecongressca.com/category/cyp/

Pharmacokinetic, pharmacodynamic and clinical profile of HIV-1 Reverse Transcriptase inhibitors. HIV-1 Reverse Transcriptase ... Pharmacokinetic, pharmacodynamic and clinical profile of HIV-1 Reverse Transcriptase inhibitors © 2022. All Rights Reserved. ... of proinflammatory cytokines restored acute morphine antinociception in nerve-injured rats and also significantly reversed the ...

http://www.remithibert.net/category/dna-ligases/

Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in ... Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug resistance in ... Title : Low rates of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor drug ... associated with nucleoside reverse transcriptase inhibitors (NRTI) and nonnucleoside reverse transcriptase inhibitors (NNRTI) ...

https://stacks.cdc.gov/view/cdc/82536

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) Learn more ,, More ,, DRUG ABBRV. GENERIC NAME. ... Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Learn more ,, More ,, DRUG ABBRV. GENERIC NAME. ... Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) * Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) ...

https://www.poz.com/drug_charts/hiv-medications?utm_campaign=301_Redirect&utm_source=aidsmeds

Reverse transcriptase inhibitors. Lamivudine (Epivir). GlaxoSmithKline. 1,000 μM. No. Zidovudine (Retrovir). GlaxoSmithKline. ...

https://wwwnc.cdc.gov/eid/content/10/4/581-t1.htm

Gupta, Riju, "Nucleoside Reverse Transcriptase Inhibitors Induced Lactic Acidosis" (2021). Tower Health Research Day. 21. https ...

https://scholarcommons.towerhealth.org/th_researchday/2021/postersession1/21/

Reverse Transcriptase Inhibitors [‎4]‎. Reverse Transcriptase Polymerase Chain Reaction [‎1]‎. Reverse Transcription [‎1]‎. ...

https://apps.who.int:80/iris/browse?rpp=20&offset=5128&etal=-1&sort_by=-1&type=mesh&starts_with_previous=R&order=ASC

Non-Nucleoside Reverse Transcriptase Inhibitor. * Non-Nucleoside Reverse Transcriptase Inhibitor * Efavirenz * Etravirine ...

https://fpnotebook.com/legacy/HIV/Pharm/Tnfvr.htm

... and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) in human plasma. Siriraj Medical Journal, 2012 Jan; 64(1): 1-6. ... and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) in human plasma.. 作者: Sangsiriwut, Kantima. Anekthananon, ... and two non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine (NVP), and efavirenz (EFV) in human plasma. ... The compounds were separated on a reversed-phase C18 column with gradient phase of 25 mM phosphate buffer (pH 4.9) and ...

https://imsear.searo.who.int/handle/123456789/138551?locale=zh_TW

Three-drug combination of a non-nucleoside reverse transcriptase inhibitor, and two nucleo(t)side reverse transcriptase ... Nucleoside or Nucleotide Reverse Transcriptase Inhibitors. Class Summary. NRTIs are nucleoside or nucleotide reverse ... CYP3A inhibitor), and emtricitabine and tenofovir alafenamide (TAF), both nucleoside analog reverse transcriptase inhibitors ( ... Nonnucleoside Reverse Transcriptase Inhibitors. Class Summary. NNRTIs inhibit both DNA-directed and RNA-directed polymerase ...

https://www.staging.medscape.com/answers/965086-161445/which-medications-in-the-drug-class-nonnucleoside-reverse-transcriptase-inhibitors-are-used-in-the-treatment-of-pediatric-hiv-infection

... reverse transcriptase (RT) have been reported. Several lines of evidence, including the isolation of RT mutants that show cross ... A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) ... A number of chemically distinct nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase ( ... Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase J Virol. 1993 ...

https://pubmed.ncbi.nlm.nih.gov/7680393/

a. Nucleoside reverse transcriptase inhibitors (NRTIs). Evidence: NRTIs do not appear to have significant risk for interactions ...

https://www.cdc.gov/mmwr/volumes/69/wr/mm6914a3.htm?s_cid=mm6914a3_w%5C

Biochemical and mechanistic basis for the activity of nucleoside analogue inhibitors of HIV reverse transcriptase. ... the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs), act ... Biochemical and mechanistic basis for the activity of nucleoside analogue inhibitors of HIV reverse transcriptase. Reverse ... reverse transcriptase, RT) ... HIV encodes an RNA directed DNA polymerase (reverse transcriptase, RT) that is an essential ...

https://polbase.neb.com/references/1719

LINE1 Reverse Transcriptase Inhibitors Abrogate Type 1 Interferon Responses , American College of Rheumatology Convergence 2022 ... Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to ...

https://rometx.com/presentations/line1-reverse-transcriptase-inhibitors-abrogate-type-1-interferon-responses-american-college-of-rheumatology-convergence-2022/

This study investigates how nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations of subtype C affect ... Replicative fitness costs of nonnucleoside reverse transcriptase inhibitor drug resistance mutations on HIV subtype C.. ... The 103N, 106A, 106M, 181C, 188C, 188L, and 190A drug resistance mutations were placed in a reverse transcriptase (RT) that ... HIV/efeitos dos fármacos HIV/genética Inibidores da Transcriptase Reversa/farmacologia Linhagem Celular Farmacorresistência ...

https://pesquisa.bvsalud.org/perinatal/resource/pt/mdl-21402856

Medications for HIV/AIDS (Nucleoside reverse transcriptase inhibitors (NRTIs)). Taking horsetail with NRTIs might reduce the ...

https://medlineplus.gov/druginfo/natural/843.html

Reverse Transcriptase Inhibitors. Nucleic Acid Synthesis Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological ...

https://clinicaltrials.gov/ct2/show/NCT02755350

Ninety-seven HIV-1-infected children who started two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (mainly zidovudine/lamivudine/nevirapine) in Mali were prospectively studied. (pasteur.fr)
Initial therapy should be started with a combination of 3 ARTs, including a backbone of 2 NRTIs plus an NNRTI, or 2 NRTIs plus a protease inhibitor. (medscape.com)
NRTIs are nucleoside or nucleotide reverse transcriptase inhibitor analogs with antiretroviral activity. (medscape.com)
Two of the four classes of currently approved anti-HIV drugs, the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs), act by inhibiting this enzyme. (neb.com)
PZA PZA include protease inhibitors, NRTIs, and NNRTIs. (cdc.gov)
Methods: In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30 000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. (elsevier.com)
NRTIs and integrase inhibitors interfere with the action of the two enzymes to prevent the virus from replicating and further infecting cells. (gsk.com)

This study investigates how nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations of subtype C affect replication capacity. (bvsalud.org)
nonnucleaoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), fusion inhibitors, integrase trans transfer inhibitors (INSTI), and CCR5 Antagonists. (homeworkshine.com)
The different classes of drug regimens include: nucleoside reverse transcriptase inhibitors (NRTI), nonnucleaoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), fusion inhibitors, integrase trans transfer inhibitors (INSTI), and CCR5 Antagonists. (homeworkshine.com)
We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. (elsevier.com)
IQR 2·8-12·9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30 000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30 000 copies per mL (NNRTI-higher). (elsevier.com)

For example, most of the HIV-1 O group viruses are considered to be naturally resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) due to the presence of the Y181C mutation [ 7 ]. (biomedcentral.com)
All non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized in the liver by CYP3A isoenzymes. (medscape.com)
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. (edu.au)
NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. (edu.au)
IMSEAR at SEARO: High performance liquid chromatographic assay for the determination of Protease Inhibitors (PIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) in human plasma. (who.int)
Objective: To develop and validate a high performance liquid chromatography (HPLC) method for simultaneous quantitative determination of five HIV protease inhibitors (PIs): indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and two non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine (NVP), and efavirenz (EFV) in human plasma. (who.int)
or or A 20%-25% increase in the dose of protease inhibitors or NNRTIs might be necessary. (cdc.gov)
INH Daily for 2 weeks and INH 2 times/week for The patient should be monitored If the patient also is taking RFB then 2 times/week for RFB 4 months (18 weeks) carefully for RFB drug toxicity efavirenz, the daily or twice (arthalgia, uveitis,leukopenia) weekly dose of RFB is increased if RFB is used concurrently from 300mg to 450 mg. with protease inhibitors or NNRTIs. (cdc.gov)
Six-month RIF-based therapy (may be prolonged* to 9 months) ------------------------------------------------------------------------------------------------------------------------------------------------------------------- A.I INH Daily for 2 months INH Daily or 2-3 times/week Protease inhibitors or NNRTIs SM is contraindicated for RIF (8 weeks) RIF for 4 months (18 weeks) should not be administered pregnant women. (cdc.gov)
However, the rapid emergence of drug-resistant strains and unsatisfactory drug-like properties seriously limit the clinical application of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). (bvsalud.org)
The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC50 = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. (bvsalud.org)
Although non-nucleoside reverse transcriptase inhibitors (NNRTIs) exhibit potent anti-HIV-1 activity and play an important role in the active antiretroviral therapy of AIDS, the emergence of drug-resistant strains has seriously reduced their clinical efficacy. (bvsalud.org)

Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. (elsevier.com)
Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. (elsevier.com)

A nucleoside analogue reverse transcriptase inhibitor (NRTI) with antiretroviral activity against HIV, it is used (particularly as the sulfate) with other antiretrovirals in combination therapy of HIV infection. (ebi.ac.uk)

Replicative fitness costs of nonnucleoside reverse transcriptase inhibitor drug resistance mutations on HIV subtype C. (bvsalud.org)

Standard reverse transcription-polymerase chain reaction (RT-PCR) can be done with INCB018424 biological activity smaller amounts of RNA (20C40 ng), but quantification is hard and relies on endpoint analysis of the PCR product. (irjs.info)

1. Rinkman K, Smeitink JA, Romijn JA, Reiss P. Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. (bvsalud.org)

The 103N, 106A, 106M, 181C, 188C, 188L, and 190A drug resistance mutations were placed in a reverse transcriptase (RT) that matches the consensus subtype C sequence as well as the HXB2 RT, as a subtype B reference. (bvsalud.org)

HIV reverse transcriptase structures: designing new inhibitors and understanding mechanisms of drug resistance. (ox.ac.uk)
Several lines of evidence, including the isolation of RT mutants that show cross resistance, suggest that, despite their structural diversity, many of these inhibitors bind to a common site on HIV-1 RT. (nih.gov)
We have used BspMI cassette mutagenesis to prepare a collection of HIV-1 RT mutants that show resistance to the known members of the general class of nonnucleoside inhibitors. (nih.gov)
This collection of mutants can be used to determine whether a new drug will show cross resistance with known inhibitors and to define amino acid positions critical for the action of the drugs. (nih.gov)
This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. (bvsalud.org)
Carbovir Triphosphate Triethylamine Salt (Abacavir - In House Impurity) is an active metabolite of Abacavir (A104990) used to study the molecular mechanism of inhibition and drug resistance for HIV-1 reverse transcriptase (1, 2, 3). (hoelzel-biotech.com)

The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0-81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. (who.int)

It inhibits activity of HIV reverse transcriptase by competing with natural substrate for use by and incorporation into viral DNA. (medscape.com)
This antiretroviral agent used in treatment of AIDS inhibits activity of HIV reverse transcriptase by competing with natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by causing DNA chain termination. (medscape.com)
An entity which inhibits the activity of HIV-1 reverse transcriptase. (ebi.ac.uk)
RNase H inhibitors have been explored as an anti-HIV drug target because RNase H inactivation inhibits reverse transcription. (unl.edu)
mTOR kinase inhibitor AZD2014 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. (biochempartner.com)

Sovaldi belongs to a group of drugs called nucleotide analog polymerase inhibitors. (rxwiki.com)
Based on drug class, the global hepatitis therapeutics market has been categorized into nucleotide analog reverse transcriptase inhibitor, NS5A inhibitor, multi- class combination, nucleotide analog NS5B polymerase inhibitor, interferon & ribavirin, and others. (clickpress.com)

Wang, H. X. and Ng, T. B. Examination of lectins, polysaccharopeptide, polysaccharide, alkaloid, coumarin and trypsin inhibitors for inhibitory activity against human immunodeficiency virus reverse transcriptase and glycohydrolases. (webmd.com)
The co-crystal structure analysis and molecular dynamics simulation studies were conducted to explain the broad-spectrum inhibitory activity of 18b1 against reverse transcriptase variants. (bvsalud.org)

It does this by using an enzyme called reverse transcriptase. (va.gov)
HIV encodes an RNA directed DNA polymerase (reverse transcriptase, RT) that is an essential enzyme in the viral replication cycle. (neb.com)
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (bvsalud.org)
In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. (bvsalud.org)
1, 2, 3 The performance of the reverse transcription (RT) response may be suffering from the enzyme, primers, nucleotides, and RNA secondary framework. (irjs.info)

In order to identify highly selective and potent BuChE inhibitors, a 53-membered compound library was constructed via the oxime-based tethering approach based on microscale synthesis. (bvsalud.org)

be detected using real-time quantitative reverse transcriptase-PCR, and this assay revealed a statistical link between hTERT mRNA levels and the aggressiveness of breast tumors [12]. (asiatox.org)

Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol. (edu.au)

Fusion inhibitors prevents HIV from entering the cells by blocking the fusion process of the virus to the membrane of the CD4 T cells. (homeworkshine.com)

This guideline presents updated data about drug interactions between protease inhibitors and non-nucleoside reverse transcriptase inhibitors for treatment of HIV infection together with rifamycins for treatment of TB. (cdc.gov)

Amplification for RT was done as follows: initial incubation step at 25 ºC for 10 min, followed by a reverse transcription step at 48 ºC for 30 min and a reverse transcriptase inactivation step at 95 ºC for 5 min in a GeneAmp® PCR system 9700 (Applied Biosystems, USA). (docsbay.net)

Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. (medscape.com)

Gupta, Riju, "Nucleoside Reverse Transcriptase Inhibitors Induced Lactic Acidosis" (2021). (towerhealth.org)

The reverse transcription (RT) reaction mixture contained 2.5 µg of total RNA, 1X TaqMan RT buffer, 5.5 mM magnesium chloride, 500 µM of each dNTP, 2.5 µM olig-dT, 0.4 U µL-1 RNase inhibitor, and 1.25 U µL-1 MultiScribe reverse transcriptase in a total reaction volume of 100 µL. (docsbay.net)
DNA polymerases, PCR Master Mixes, qPCR Mixes and reverse transcription reagents are highly valued across the globe. (solisbiodyne.com)

Treatment with telomerase inhibitors may not have the toxicity found with other chemotherapeutic brokers since telomerase is usually absent in most somatic cells (Fig. (asiatox.org)

The twice-weekly dose of RFB (300mg) remains unchanged if the patient is also taking these protease inhibitors. (cdc.gov)

Guidelines for the Use of Rifabutin or Rifampin for the Treatment and Prevention of Tuberculosis among HIV-Infected Patients Taking Protease Inhibitors or Non-Nucleoside Reverse Transcriptase Inhibitors. (cdc.gov)

Reference: Biochemical and mechanistic basis for the activity of nucleoside analogue inhibitors of HIV reverse transcriptase. (neb.com)
Vistusertib, also known as AZD2014, is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. (biochempartner.com)

HIV-1 reverse transcriptase is one of the most attractive targets for the treatment of AIDS. (bvsalud.org)
Since most breast cancer cells have very short telomeres, treatment with telomerase inhibitors should lead to growth arrest and cell death. (asiatox.org)

971 adults on Non-Nucleoside Reverse Transcriptase Inhibitors were included. (academicjournals.org)

To study the role of reverse transcriptase dimerization in HIV replication. (edu.au)
Protease inhibitors target the cell replication in the later stages. (homeworkshine.com)
Further, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, has been detected in kidney biopsy samples from patients with HIVAN, suggesting active replication in renal tissue. (medscape.com)

HIV reverse transcriptase (RT) is one of the main targets for the action of anti-AIDS drugs. (ox.ac.uk)
These analyses suggest that all three drugs interact with HIV-1 RT within the previously defined common binding site for nonnucleoside inhibitors. (nih.gov)

Anatomy6

Organisms9

Diseases9

Chemicals and Drugs71

Analytical, Diagnostic and Therapeutic Techniques and Equipment27

Psychiatry and Psychology1

Phenomena and Processes32

Disciplines and Occupations1

Information Science5

Health Care9

Geographicals2

Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells. (1/2177)

Safety and pharmacokinetics of abacavir (1592U89) following oral administration of escalating single doses in human immunodeficiency virus type 1-infected adults. (2/2177)

Safety and single-dose pharmacokinetics of abacavir (1592U89) in human immunodeficiency virus type 1-infected children. (3/2177)

Suppression of replication of multidrug-resistant HIV type 1 variants by combinations of thymidylate synthase inhibitors with zidovudine or stavudine. (4/2177)

Functional analysis of mutations conferring lamivudine resistance on hepatitis B virus. (5/2177)

The cost-effectiveness of treatment with lamivudine and zidovudine compared with zidovudine alone: a comparison of Markov model and trial data estimates. (6/2177)

Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. (7/2177)

Genotypic resistance and the treatment of HIV-1 infection in Espirito Santo, Brazil. (8/2177)

Reverse Transcriptase Inhibitors

HIV Reverse Transcriptase

Anti-HIV Agents

Drug Resistance, Viral

HIV-1

Benzoxazines

Nevirapine

HIV Infections

Zidovudine

Delavirdine

HIV Protease Inhibitors

RNA-Directed DNA Polymerase

Organophosphonates

Stavudine

Dideoxynucleosides

Drug Resistance, Multiple, Viral

Adenine

Oxazines

Didanosine

Antiretroviral Therapy, Highly Active

Lamivudine

Pyrimidinones

Pyridazines

Pyranocoumarins

Nucleosides

Ritonavir

Zalcitabine

Lopinavir

Dideoxynucleotides

Viral Load

Anti-Retroviral Agents

HIV

CD4 Lymphocyte Count

Drug Therapy, Combination

RNA, Viral

Mutation

Treatment Failure

Virus Replication

HIV Protease

Nelfinavir

Ribonuclease H

HIV Integrase Inhibitors

HIV-Associated Lipodystrophy Syndrome

Telomerase

Reverse Transcriptase Polymerase Chain Reaction

Antiviral Agents

Drug Interactions

Molecular Sequence Data

Thymine Nucleotides

Acidosis, Lactic

Reverse Transcription

pol Gene Products, Human Immunodeficiency Virus

Mutation, Missense

Integrase Inhibitors

Genotype

Furans

HIV-2

Saquinavir

Indinavir

Pyrrolidinones

Acquired Immunodeficiency Syndrome

Base Sequence

Nitriles

Drug Resistance, Microbial

Anilides

Cell Line

Benzoxazoles

Amino Acid Substitution

Pyridines

Inhibitory Concentration 50

Protease Inhibitors

Pyridones

Avian myeloblastosis virus

Lipodystrophy

Foscarnet

DNA, Viral

Erythrocebus patas

DNA, Mitochondrial

Sulfur Compounds

Area Under Curve