Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).HIV Protease Inhibitors: Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.HIV Protease: 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.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Secretory Leukocyte Peptidase Inhibitor: A proteinase inhibitor found in various BODILY SECRETIONS that coat mucosal surfaces such as SEMINAL PLASMA; CERVICAL MUCUS; and bronchial secretions. It plays a role in protecting epithelial tissues from LEUKOCYTE-derived serine proteases such as NEUTROPHIL ELASTASE.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Saquinavir: 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.Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.Proteinase Inhibitory Proteins, Secretory: Peptides and proteins found in BODILY SECRETIONS and BODY FLUIDS that are PROTEASE INHIBITORS. They play a role in INFLAMMATION, tissue repair and innate immunity (IMMUNITY, INNATE) by inhibiting endogenous proteinases such as those produced by LEUKOCYTES and exogenous proteases such as those produced by invading microorganisms.Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.Cysteine Proteases: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Molecular Sequence Data: 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.Amino Acid Sequence: 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.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Carbamates: 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.Lopinavir: An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.PyrimidinonesDrug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Aprotinin: A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)Protease La: A prokaryotic ATP-dependent protease that plays a role in the degradation of many abnormal proteins. It is a tetramer of 87-kDa subunits, each of which contains a proteolytic site and a ATP-binding site.Tosyllysine Chloromethyl Ketone: An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process.Gabexate: A serine proteinase inhibitor used therapeutically in the treatment of pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant for hemodialysis. The drug inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, but not of chymotrypsin and aprotinin.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.ATP-Dependent Proteases: Proteases that contain proteolytic core domains and ATPase-containing regulatory domains. They are usually comprised of large multi-subunit assemblies. The domains can occur within a single peptide chain or on distinct subunits.Oligopeptides: Peptides composed of between two and twelve amino acids.Trypsin Inhibitor, Bowman-Birk Soybean: A low-molecular-weight protein (minimum molecular weight 8000) which has the ability to inhibit trypsin as well as chymotrypsin at independent binding sites. It is characterized by a high cystine content and the absence of glycine.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Pepstatins: N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.Anti-HIV Agents: 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.Antipain: An oligopeptide produced by various bacteria which acts as a protease inhibitor.Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Tosylphenylalanyl Chloromethyl Ketone: An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.Trypsin Inhibitor, Kunitz Soybean: A high-molecular-weight protein (approximately 22,500) containing 198 amino acid residues. It is a strong inhibitor of trypsin and human plasmin.Cystatins: A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 22.214.171.124.Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 126.96.36.199.Kinetics: The rate dynamics in chemical or physical systems.Serpin E2: A protease nexin and serpin subtype that is specific for several SERINE PROTEASES including UROKINASE; THROMBIN; TRYPSIN; and PLASMINOGEN ACTIVATORS.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 188.8.131.52.Mutation: 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.Drug Resistance, Multiple, Viral: 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.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Serine Proteases: Peptide hydrolases that contain at the active site a SERINE residue involved in catalysis.Sulfonamides: A group of compounds that contain the structure SO2NH2.Molecular Weight: The sum of the weight of all the atoms in a molecule.Subtilisins: A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-Antiretroviral Therapy, Highly Active: 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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cell Line: Established cell cultures that have the potential to propagate indefinitely.alpha-Macroglobulins: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.Elafin: A secretory proteinase inhibitory protein that was initially purified from human SKIN. It is found in a variety mucosal secretions and is present at high levels in SPUTUM. Elafin may play a role in the innate immunity (IMMUNITY, INNATE) response of the LUNG.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 184.108.40.206.Cathepsin L: A ubiquitously-expressed cysteine protease that plays an enzymatic role in POST-TRANSLATIONAL PROTEIN PROCESSING of proteins within SECRETORY GRANULES.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Cathepsin G: A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.Trypsin Inhibitor, Kazal Pancreatic: A pancreatic trypsin inhibitor common to all mammals. It is secreted with the zymogens into the pancreatic juice. It is a protein composed of 56 amino acid residues and is different in amino acid composition and physiological activity from the Kunitz bovine pancreatic trypsin inhibitor (APROTININ).Viral Nonstructural Proteins: Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.Chymases: A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Viral Load: 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.Methylurea Compounds: Urea compounds which are substituted with one or more methyl groups.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Pyrones: Keto-pyrans.Cells, Cultured: 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.Antiviral Agents: 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.Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC 220.127.116.11.alpha 1-Antichymotrypsin: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 18.104.22.168), TISSUE KALLIKREIN (EC 22.214.171.124), and PROSTATE-SPECIFIC ANTIGEN (EC 126.96.36.199).Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Tryptases: A family of neutral serine proteases with TRYPSIN-like activity. Tryptases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Protein PrecursorsProteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Structure-Activity Relationship: 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.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Ubiquitin-Specific Proteases: Members of the peptidase C19 family which regulate signal transduction by removing UBIQUITIN from specific protein substrates via a process known as deubiquitination or deubiquitylation.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.CD4 Lymphocyte Count: The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 188.8.131.52.Fibrinolysin: A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.Cystatin A: A cytastin subtype found at high levels in the SKIN and in BLOOD CELLS. Cystatin A incorporates into the cornified cell envelope of stratified squamous epithelial cells and may play a role in bacteriostatic properties of skin.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.alpha 1-Antitrypsin Deficiency: Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.Endopeptidase Clp: An ATP-dependent protease found in prokaryotes, CHLOROPLASTS, and MITOCHONDRIA. It is a soluble multisubunit complex that plays a role in the degradation of many abnormal proteins.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Bacterial Proteins: Proteins found in any species of bacterium.Amino Acid Chloromethyl Ketones: Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.Metalloproteases: Proteases which use a metal, normally ZINC, in the catalytic mechanism. This group of enzymes is inactivated by metal CHELATORS.Dipeptides: Peptides composed of two amino acid units.Macrocyclic Compounds: Cyclic compounds with a ring size of approximately 1-4 dozen atoms.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.RNA, Messenger: 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.Caspase 1: A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.Factor XIa: Activated form of factor XI. In the intrinsic pathway, Factor XI is activated to XIa by factor XIIa in the presence of cofactor HMWK; (HIGH MOLECULAR WEIGHT KININOGEN). Factor XIa then activates factor IX to factor IXa in the presence of calcium.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Amino Acid Substitution: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.SulfonesVirus Replication: 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.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Complement C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Cathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Hepacivirus: A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Benzamidines: Amidines substituted with a benzene group. Benzamidine and its derivatives are known as peptidase inhibitors.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.HIV: 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.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Drug Design: 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.Periplasmic Proteins: Proteins found in the PERIPLASM of organisms with cell walls.Protein C Inhibitor: A member of the serpin family of proteins that is found in plasma and urine. It is dependent on heparin and is able to inhibit activated PROTEIN C; THROMBIN; KALLIKREIN; and other SERINE ENDOPEPTIDASES.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Isoflurophate: A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Oxazines: Six-membered heterocycles containing an oxygen and a nitrogen.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Granzymes: A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.Benzoxazines: OXAZINES with a fused BENZENE ring.HIV Reverse Transcriptase: 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.Viral Proteins: Proteins found in any species of virus.Leucine: An essential branched-chain amino acid important for hemoglobin formation.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Inhibitory Concentration 50: 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.DNA Primers: 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.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Hemolymph: The blood/lymphlike nutrient fluid of some invertebrates.Antithrombin III: A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.gag Gene Products, Human Immunodeficiency Virus: Proteins encoded by the GAG GENE of the HUMAN IMMUNODEFICIENCY VIRUS.Factor Xa: Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors.Arthropod Proteins: Proteins synthesized by organisms belonging to the phylum ARTHROPODA. Included in this heading are proteins from the subdivisions ARACHNIDA; CRUSTACEA; and HORSESHOE CRABS. Note that a separate heading for INSECT PROTEINS is listed under this heading.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Anti-Retroviral Agents: Agents used to treat RETROVIRIDAE INFECTIONS.Furin: A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.Molecular Structure: 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.Proprotein Convertases: Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.Cathepsin D: An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 184.108.40.206. (Formerly EC 220.127.116.11).Lipodystrophy: 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.Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Zidovudine: 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.Chromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Enzyme Stability: The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.HIV-Associated Lipodystrophy Syndrome: 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.Urokinase-Type Plasminogen Activator: A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Factor XIIa: Activated form of factor XII. In the initial event in the intrinsic pathway of blood coagulation, kallikrein (with cofactor HIGH MOLECULAR WEIGHT KININOGEN) cleaves factor XII to XIIa. Factor XIIa is then further cleaved by kallikrein, plasmin, and trypsin to yield smaller factor XII fragments (Hageman-Factor fragments). These fragments increase the activity of prekallikrein to kallikrein but decrease the procoagulant activity of factor XII.pol Gene Products, Human Immunodeficiency Virus: Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.Caseins: A mixture of related phosphoproteins occurring in milk and cheese. The group is characterized as one of the most nutritive milk proteins, containing all of the common amino acids and rich in the essential ones.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Guanidines: A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Alpha-Globulins: Serum proteins that have the most rapid migration during ELECTROPHORESIS. This subgroup of globulins is divided into faster and slower alpha(1)- and alpha(2)-globulins.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Endogenous plasma protease inhibitors deactivate drotrecogin. Therefore, no dose adjustment is needed in elderly patients, or ... The United States' Food and Drug Administration (FDA) approved the drug in 2001 as was the case with the drug authorities in ... Information (PDF) on the drug from the Food and Drug Administration (FDA). ... Factor Xa inhibitors. (with some II inhibition). Heparin group/. glycosaminoglycans/. (bind antithrombin). *Low molecular ...
HIV protease inhibitors; the antidepressant nefazodone; the cardiovascular drug gemfibrozil; the immunosuppressant ciclosporin ... Tobert JA (2003). "Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors". Nat Rev Drug Discov. 2 (7): 517-26 ... to sell simvastatin as an authorized generic drug. List of drugs affected by grapefruit "Simvastatin". The ... Reduced maximum doses of simvastatin apply for patients taking certain other drugs, including the cardiovascular drugs ...
... is a hepatitis C virus protease inhibitor. Faldaprevir was tested in combination regimens with pegylated interferon ... Boehringer announced in 2014 that it would not pursue approval of the drug any more because of better HCV treatments having ... Faldaprevir was an experimental drug for the treatment of hepatitis C (HCV). It was being developed by Boehringer-Ingelheim and ...
Nixon, AE; Wood, CR (2006). "Engineered protein inhibitors of proteases". Current Opinion in Drug Discovery & Development. 9 (2 ... Salier JP (1990). "Inter-alpha-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily ... Examples of Kunitz-type protease inhibitors are aprotinin (bovine pancreatic trypsin inhibitor, BPTI), Alzheimer's amyloid ... or basic protease inhibitor), but the family includes numerous other members, such as snake venom basic protease; mammalian ...
Important antiretroviral drugs include the class of protease inhibitors. Herpes viruses, best known for causing cold sores and ... Antibacterials are among the most commonly used drugs and among the drugs commonly misused by physicians, for example, in viral ... Some of these side effects can be life-threatening if the drug is not used properly. As well as their use in medicine, ... The drug toxicity to humans and other animals from antibacterials is generally considered low.(depends) ...
"New approaches to structure-based discovery of dengue protease inhibitors". Infectious Disorders Drug Targets. 9 (3): 327-43. ... Secondly, it may be possible to develop specific inhibitors of the viral protease (coded by NS3), which splices viral proteins ... Finally, it may be possible to develop entry inhibitors, which stop the virus entering cells, or inhibitors of the 5′ capping ... Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen should not be used. Dengue has become a global problem since ...
Drugs of the Future, Volume 22, Issue 4, April 1997; Nelfinavir Mesylate. Antiviral for AIDS, HIV-1 protease inhibitor. X. ... Nelfinavir is a protease inhibitor: it inhibits HIV-1 and HIV-2 proteases. HIV protease is an aspartate protease which splits ... All protease inhibitors bind to the protease, the precise mode of binding determines how the molecule inhibits the protease. ... Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in ...
HIV - Simple English Wikipedia, the free encyclopedia
Protease Inhibitors (PIs) *Metabolic abnormalities including dyslipidemia, hyperglycemia, insulin resistance, and lipodystrophy ... Needle-sharing injection drug use [People sharing the same needle to inject illegal drugs] 67 (0.67%) ... This means a person takes a drug before having risky sex. The drug 'Truvada' is a combination of two different anti-viral ... Negative side effects can vary by drug, by ethnicity, and by drug interactions in the body. The following list contains the ...
Protease inhibitors found in HIV drugs are linked to insulin resistance. At the cellular level, much of the variance in insulin ... Fantry, Lori E (2003-03-24). "Protease Inhibitor-Associated Diabetes Mellitus: A Potential Cause of Morbidity and Mortality". ... Certain drugs also may be associated with insulin resistance (e.g., glucocorticoids). The presence of insulin ... Beyond vascular complications". Endocrine, Metabolic & Immune Disorders Drug Targets. 11 (2): 132-40. doi:10.2174/ ...
Reversion of lipodystrophy does not occur after withdrawal of protease inhibitors. Lipodystrophy Drug-induced lipodystrophy ... On the one hand, lipodystrophy seems to be mainly due to HIV-1 protease inhibitors. Interference with lipid metabolism is ... February 2001). "Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study ... Also, the development of lipodystrophy is associated with specific nucleoside reverse transcriptase inhibitors (NRTI). ...
Drugs developed include amprenavir, an HIV protease inhibitor; telaprevir, a protease inhibitor for treatment of hepatitis C; ... He initially worked on hypertension drugs, developing a highly potent renin inhibitor. An important step in this process was ... Agenerase (amprenavir), an HIV protease inhibitor, was co-developed by Vertex and GlaxoSmithKline for the treatment of HIV/Aids ... Vertex also developed Telaprevir, a protease inhibitor for treatment of hepatitis C. Telaprevir works by disabling a protein ...
There is a large class of drugs called protease inhibitors that inactivate this enzyme. ... Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target ... Detection and significance of minority quasispecies of drug-resistant HIV-1. Journal of HIV Therapy. 2006;11(4):74-81. PMID ... However, there is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. ...
... has the ability to inhibit the replication of viruses that are resistant to other protease inhibitors and it ... The drug has also been shown to cause increases in total cholesterol and triglycerides. Aptivus labeling has a black box ... Tipranavir (TPV), or tipranavir disodium, is a nonpeptidic protease inhibitor (PI) manufactured by Boehringer Ingelheim under ... "Selection and Characterization of HIV-1 Showing Reduced Susceptibility to the Non-Peptidic Protease Inhibitor Tipranavir". ...
Synergistic enhancer (antiretroviral)
It enhances other protease inhibitors through the inhibition of CYP3A4, a liver enzyme. While ritonavir is a protease inhibitor ... The mechanism underlying the effects of chloroquine on response to protease inhibitorsis inhibition of cellular drug efflux ... By pre-treating with grapefruit juice prior to taking protease inhibitors the GI intake and therefore the bioavailabity is ... Chloroquine/quinoline antimalarials Chloroquine is being investigated as a synergistic enhancer of protease inhibitors. ...
There is a large class of drugs called protease inhibitors that inactivate this enzyme. Hepatitis C is caused by an RNA virus. ... Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different ... Antiviral drugs are often nucleoside analogues (fake DNA building-blocks), which viruses mistakenly incorporate into their ... Antibiotics have no effect on viruses, but several antiviral drugs have been developed. The word is from the Latin neuter vīrus ...
It is a member of a class of antiviral drugs known as protease inhibitors. Specifically, telaprevir inhibits the hepatitis C ... and reversible inhibitor of hepatitis C virus NS3.4A serine protease". Infect Disord Drug Targets. 6 (1): 3-16. doi:10.2174/ ... Kim, Jenny; Culley, Colleen; Mohammad Rima, Telaprevir (2012). "An Oral Protease Inhibitor for Hepatitis C Virus Infection". Am ... in combination with drugs peginterferon alfa and ribavirin (Incivek combination treatment), the US Food and Drug Administration ...
... such as protease inhibitors, which include drugs against AIDS and hypertension. These protease inhibitors bind to an enzyme's ... Schechter I (2005). "Mapping of the active site of proteases in the 1960s and rational design of inhibitors/drugs in the 1990s ... Active sites can be mapped to aid design of new drugs such as enzyme inhibitors. This involves description of the size of an ... An important factor in drug design is the strength of binding between the active site and an enzyme inhibitor. ...
The first HIV protease inhibitor approved by the FDA was saquinavir, which was designed to target wild-type HIV-1 protease. ... "Investigation on the mechanism for the binding and drug resistance of wild type and mutations of G86 residue in HIV-1 protease ... It is of the protease inhibitor (PI) class and works by blocking HIV protease. Darunavir was approved for medical use in the ... However, this inhibitor is no longer effective due to resistance-causing mutations on the HIV-1 protease structure. The HIV ...
... is an analog of the already approved HIV protease inhibitor, saquinavir. HIV protease inhibitor drugs not only work ... However, these drugs tend to have many toxic effects. Adding a nitrate ester functional group to HIV protease inhibitors has ... OX1001 is a nitrate ester analog of the approved HIV protease inhibitor, saquinavir. This modification increases the anti- ... "The new and less toxic protease inhibitor saquinavir-NO maintains anti-HIV-1 properties in vitro indistinguishable from those ...
The HIV protease inhibitor Tipranavir is marketed for the treatment of AIDS. The first enantioselective medicinal chemistry ... Jamali, Fakhreddin (1993). "Chapter 14: Stereochemically Pure Drugs: An Overview". In Wainer, Irving W. Drug Stereochemistry: ... 1998). "Tipranavir (PNU-140690): A Potent, Orally Bioavailable Nonpeptidic HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy- ... 1991). "Inhibitors of Cholesterol Biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-( lH-pyrrol-l-yl)ethyl]-2H-pyran-2-one Inhibitors ...
"New approaches to structure-based discovery of dengue protease inhibitors". Infectious Disorders Drug Targets. 9 (3): 327-43. ... Secondly, it may be possible to develop specific inhibitors of the viral protease (coded by NS3), which splices viral proteins. ... 96] Finally, it may be possible to develop entry inhibitors, which stop the virus entering cells, or inhibitors of the 5′ ... Apart from attempts to control the spread of the Aedes mosquito there are ongoing efforts to develop antiviral drugs that would ...
... ribavirin and recently approved protease inhibitors such as Telaprevir (Incivek) May 2011, Boceprevir (Victrelis) May 2011 or ... These PEGylated drugs are injected once weekly, rather than administering two or three times per week, as is necessary for ... Interferon-containing regimens may also include protease inhibitors such as boceprevir and telaprevir. Interferons were first ... Both hepatitis B and hepatitis C are treated with IFN-α, often in combination with other antiviral drugs. Some of those treated ...
Interactions with drugs with narrow therapeutic windows like warfarin, ciclosporin, protease inhibitors and cardiac glycosides ... However, it is not yet known whether goldenseal contains a drug resistance efflux pump inhibitor, although many antimicrobial ... Subjects who drank large amounts of water had the same urine drug levels as subjects who took goldenseal capsules along with ... It appears likely that goldenseal shares with Mahonia (Oregon grape) and Berberis (Barberry) the ability to inhibit the drug ...
One group of drugs that efavirenz affects is protease inhibitors, which are used for HIV/AIDS. Efavirenz will lower the blood ... At lowered levels, protease inhibitors may not be effective in people taking both drugs, which means the virus that causes HIV/ ... Similar to the effect seen with protease inhibitors, efavirenz lowers the blood levels of antifungal drugs like voriconazole, ... People who are taking both efavirenz and other drugs metabolized by the same enzymes might need the dose of their drugs to be ...
... like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of ... It is the first multi-drug capsule to contain a drug not available individually. Lopinavir/ritonavir was approved by the USA ... researchers found the points of attack of the HIV protease inhibitors - agents that block the breakdown of proteins. Protease ... Both medications are HIV protease inhibitors. Ritonavir functions by slowing down the breakdown of lopinavir. Lopinavir/ ...
... is a drug for the treatment of HIV infections. It is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. ... Amprenavir is a HIV protease inhibitor. Eron J Jr; Yeni P; Gathe J Jr; et al. (2006). "The KLEAN study of fosamprenavir- ... "Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters". FEBS Journal. 277 (18 ... ISBN 978-3-85200-181-4. Drugs.com: Lexiva Monograph. Shen, C. H.; Wang, Y. F.; Kovalevsky, A. Y.; Harrison, R. W.; Weber, I. T ...
These drugs include statins, HIV protease inhibitors, many calcium channel blockers, lidocaine, the benzodiazepines, and ... "Abbreviated New Drug Application (ANDA): 204154". Drugs@FDA: FDA Approved Drug Products. U.S. Food and Drug Administration. ... Saunders Handbook of Veterinary Drugs: Small and Large Animal (4 ed.). Elsevier Health Sciences. 2015. p. 420. ISBN 978-0-323- ... Ivermectin is available as a generic prescription drug in the U.S. in a 3 mg tablet formulation. It is also sold under the ...
Common Drug Interactions with Protease Inhibitors: Overview, Drug Interactions by Drug Category
Drug interactions with antiretrovirals are commonly caused by the inhibition or induction of hepatic drug metabolism. ... Potential for drug interactions should be considered when selecting antiretroviral therapy (ART) for patients infected with the ... encoded search term (Common Drug Interactions with Protease Inhibitors) and Common Drug Interactions with Protease Inhibitors ... How do HMG-CoA reductase inhibitors and protease inhibitors (PIs) interact?. How do PDE5 inhibitors and protease inhibitors ( ...
AIDS and HIV: The steroid connection:Protease inhibitors: Miracle drugs or not? - Healthy.net
... protease inhibitors were the Great White Hope of AIDS therapy. These drugs work by inhibiting the enzyme protease, which is ... AIDS and HIV: The steroid connection:Protease inhibitors: Miracle drugs or not?. What Doctors Dont Tell You2 min read ... The latest reports on protease inhibitors are similar to those on AZT, first launched as the drug that was going to cure AIDS ... like a protease inhibitor, and throw in yet another DNA chain terminator, like 3TC, then its a wonder drug, said Dr Peter ...
The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. - PubMed - NCBI
The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors.. Kim RB1, Fromm MF, ... Currently available HIV-1 protease inhibitors are potent agents in the therapy of HIV-1 infection. However, limited oral ... This raises the possibility that higher HIV-1 protease inhibitor concentrations may be obtained by targeted pharmacologic ...
Effect of HIV Protease Inhibitor Drugs on Glucose and Insulin Metabolism - Full Text View - ClinicalTrials.gov
HIV Protease Inhibitors. Protease Inhibitors. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Anti-HIV ... Effect of HIV Protease Inhibitor Drugs on Glucose and Insulin Metabolism. The safety and scientific validity of this study is ... This study examined the effects of two commonly prescribed HIV drugs on the way the body metabolizes glucose, insulin and fat. ...
RCSB PDB - 1K6T: LACK OF SYNERGY FOR INHIBITORS TARGETING A MULTI-DRUG RESISTANT HIV-1 PROTEASE
Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease.. King, N.M., Melnick, L., Prabu-Jeyabalan, M., ... LACK OF SYNERGY FOR INHIBITORS TARGETING A MULTI-DRUG RESISTANT HIV-1 PROTEASE. *DOI: 10.2210/pdb1K6T/pdb ... consideration is necessary to develop inhibitors that bind sufficiently tightly to drug-resistant variants of HIV-1 protease to ... On close examination, the structural rearrangements in the protease that occur in the tightest binding inhibitor complex are ...
InterMune to Present Four Abstracts on HCV Protease Inhibitor ITMN-191 at the AASLD Meeting - Drugs.com MedNews
Poster #1885: Combination of the NS3/4A Protease Inhibitor ITMN-191 (R7227) with the Active Moiety of the NS5B Inhibitors R1626 ... Home › News › Clinical Trials › InterMune to Present Four Abstracts on HCV Protease Inhibitor ITMN-191 at the AASLD Meeting ... InterMune to Present Four Abstracts on HCV Protease Inhibitor ITMN-191 at the AASLD Meeting. Print this page ... ITMN-191 is a hepatitis C virus (HCV) NS3 protease inhibitor, currently in a Phase 1b clinical trial in combination with ...
Two New Protease Inhibitors Approved By FDA: NIAID Research Was Pivotal to Development of New Class of Drugs | News | AIDSinfo
... approved the second and third of a new class of drugs called protease inhibitors. Protease inhibitors are compounds that block ... Two New Protease Inhibitors Approved By FDA: NIAID Research Was Pivotal to Development of New Class of Drugs. ... Two New Protease Inhibitors Approved By FDA: NIAID Research Was Pivotal to Development of New Class of Drugs ... Drug interactions with rifabutin and ketoconazole have been reported.. The first licensed protease inhibitor, saquinavir ( ...
European Medicines Agency informs doctors and patients about drug interaction between Victrelis and ritonavir-boosted HIV...
European Medicines Agency informs doctors and patients about drug interaction between Victrelis ritonavir-boosted HIV protease ... Questions and answers on drug interactions between Victrelis (boceprevir) and ritonavir-boosted HIV protease inhibitors (PDF/ ... with information about drug interactions between this hepatitis C medicine and the ritonavir-boosted HIV protease inhibitors ... Agency informs doctors and patients about drug interaction between Victrelis and ritonavir-boosted HIV protease inhibitors. ...
In Vitro Evaluation of the Disposition of A Novel Cysteine Protease Inhibitor | Drug Metabolism & Disposition
In Vitro Evaluation of the Disposition of A Novel Cysteine Protease Inhibitor. Wolfgang Jacobsen, Uwe Christians and Leslie Z. ... In Vitro Evaluation of the Disposition of A Novel Cysteine Protease Inhibitor. Wolfgang Jacobsen, Uwe Christians and Leslie Z. ... In Vitro Evaluation of the Disposition of A Novel Cysteine Protease Inhibitor. Wolfgang Jacobsen, Uwe Christians and Leslie Z. ... In Vitro Evaluation of the Disposition of A Novel Cysteine Protease Inhibitor ...
Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans | Drug Metabolism & Disposition
HCV NS3-4A protease is essential for the viral replication process (Lin, 2006; Moradpour et al., 2007) and is a validated drug ... Metabolism and Disposition of the Hepatitis C Protease Inhibitor Paritaprevir in Humans. Jianwei Shen, Michael Serby, Aimee ... 2015) In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450 ... Paritaprevir (also known as ABT-450), a potent NS3-4A serine protease inhibitor [identified by AbbVie (North Chicago, IL) and ...
New protease inhibitor offers patients efficacy, convenience | Drug Topics
Clinicians will soon be able to offer HIV-positive patients a protease inhibitor (PI) that combines the convenience of flexible ... New protease inhibitor offers patients efficacy, convenience. Drug Topics Nov. 17, 2003;147:23.. ... New protease inhibitor offers patients efficacy, convenience Clinicians will soon be able to offer HIV-positive patients a ... protease inhibitor (PI) that combines the convenience of flexible dosing with no restrictions on food or water. The Food & Drug ...
Hepatitis C Virus NS3/4A Protease Inhibitor global drug patents, pharmaceutical manufacturers and generics
Generic options for Hepatitis C Virus NS3/4A Protease Inhibitor pharmaceutical drugs, including patent status, patent ... Hepatitis C Virus NS3/4A Protease Inhibitor Drug Class List. ➠ Get the DrugPatentWatch Daily Briefing. » See Plans and Pricing ... Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of ...
Chain A, Lack Of Synergy For Inhibitors Targeting A Multi-drug Resistant Hiv-1 Protease (Human immunodeficiency virus 1) |...
synthetic anti-HIV drugs, protease inhibitors, potent natural anti-HIV agents - Begell House Digital Library
The frequencies of naturally occurring protease inhibitor resistance mutations in HIV proviral sequences of drug naïve sex...
The frequencies of naturally occurring protease inhibitor resistance mutations in HIV proviral sequences of drug naïve sex ... We examined protease inhibitor (PI) resistance mutations in ART naïve HIV-1 seropositive women from Pumwani sex worker cohort, ... We have analyzed consensus sequences of HIV protease from 234 drug naïve patients, as a part of HIV-1 whole genome sequencing ... However, drug resistance mutations reduce the effectiveness of ART, and need to be monitored for effective ART. Naturally ...
Structural analyses of 2015-updated drug-resistant mutations in HIV-1 protease: an implication of protease inhibitor cross...
... analyses of recent clinical mutations on the drug cross-resistance effects from various protease and protease inhibitors (PIs) ... Numerous new drugs have been developed over the past few decades but viral resistances to these drugs in the targeted viral ... While structural understanding of the viral protease and its drug resistance mutations have been well established, the ... Using the 2015 updated clinical HIV protease mutations, we constructed a structure-based correlation network and a minimum- ...
A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in...
Adult, CD4 Lymphocyte Count, Drug Monitoring, Female, Follow-Up Studies, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans ... A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in ... A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in ... BACKGROUND: We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease ...
Phase 1 Single Dose Studies to Optimize the Pharmacokinetics of DG17, a Novel HIV-Protease Inhibitor Pro-Drug, Using Sodium...
Title: Phase 1 Single Dose Studies to Optimize the Pharmacokinetics of DG17, a Novel HIV-Protease Inhibitor Pro-Drug, Using ... Phase 1 Single Dose Studies to Optimize the Pharmacokinetics of DG17, a Novel HIV-Protease Inhibitor Pro-Drug, Using Sodium ... Keywords:HIV, protease inhibitor, gastric acid neutralization, pharmacoenhancement. Abstract: DG17 is an orally available ... DG17 is an orally available prodrug of DG35 (a novel HIV protease inhibitor with variable pharmacokinetics). These studies ...
Plasma Protease C1-inhibitor Treatment Market by Dosage Type, Drug Class & Forecast - 2025 | Transparency Market Research
C1-inhibitor, Kallikrein Inhibitor, Selective Bradykinin B2 Receptor Antagonist), Dosage Type, (Lyophilized and Liquid/ ... Plasma Protease C1-inhibitor Treatment Market report categorizes the global market by Drug Class ( ... Plasma Protease C1-inhibitor Treatment Market (Drug Class- C1-inhibitors (C1-esterase Inhibitor and Recombinant Inhibitor), ... Based on drug class, the global plasma protease C1-inhibitor market is classified into C1-inhibitor, Kallikrein inhibitor, and ...
Incidence of and Risk Factors for Adverse Drug Reactions in a Prospective Cohort of HIV-Infected Adults Initiating Protease...
A second wave of protease inhibitors are in phase II and III trials and promise to provide a drug regimen with a better dosing ... asunaprevir; daclatasvir; faldaprevir; simeprevir; NS5A inhibitors; NS5B polymerase inhibitors; protease inhibitors; ribavirin ... Other direct-acting antiviral agents, including second-generation protease inhibitors, polymerase inhibitors, NS5A inhibitors, ... The future of protease inhibitors lies in the further development of second-generation drugs with a broad genotypic coverage ...
Standard Dosing Chart for Anti-HIV Drugs - TheBody.com
Cannot be taken within 2 hours of drugs that require an acidic stomach environment, including many protease inhibitors and ... Interacts with many protease inhibitors. Consult the prescription packet for information.. Patient Assistance Program: 1-800- ... Dosing scheme #1, without protease inhibitor (PI) resistance (2x/day): one pill = 700mg; TDD = 2,800mg. ... Designed to work in people whose virus has developed resistance to other protease inhibitors. ...
The HIV/AIDS Drug Pipeline - TheBody.com
Protease Inhibitors. Atazanavir Atazanavir (Zrivada, formerly known as BMS-232632) is the first PI drug likely to be taken once ... Drug Name. Drug Class. Benefits. Drawbacks. Most Likely to Use. T-20 (enfuvirtide, Fuzeon). Fusion inhibitor. Effective against ... Approved Drug Classes. A handful of experimental therapies in the three approved classes -- protease inhibitors (PIs), non- ... Entry Inhibitors. Ideally, the problems of drug resistance within and across the three approved drug classes would be overcome ...
Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a Potent, Multi-Genotypic Protease Inhibitor for the...
Drugs.com Mobile Apps. The easiest way to lookup drug information, identify pills, check interactions and set up your own ... a nucleotide inhibitor), IDX320 (a protease inhibitor), IDX375 (a non-nucleoside inhibitor) and a prototype Idenix NS5A ... IDX320 is a potent inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and 4a (IC(50) values from 0.8 to 1.9 nM), as well ... Lallos, et al, "In Vitro Antiviral Activity of IDX320, a Novel and Potent Macrocyclic HCV Protease Inhibitor", Poster #768.). ...
Foster child drug trials - SourceWatch
The studies used the standard AIDS drugs: nucleoside analogues, protease inhibitors and Nevirapine. ... All kinds of drugs." Description of drug trials. To read the list of drug studies conducted at ICC and sponsored by government ... There are dozens of drug studies in which patients have died, specifically because of the drugs. According to the drugs own ... Protease inhibitors interfere with the bodys ability to build new proteins. Since were made of protein, they have pronounced ...
SSRN International Conference on Drug Discovery (ICDD) 2020
Design and Development of Dengue Protease Inhibitors Proceedings of International Conference on Drug Discovery (ICDD) 2020 ... Insight Into Designing of Renin Inhibitors Proceedings of International Conference on Drug Discovery (ICDD) 2020 ... Insilico Approach for Identification of Novel Inhibitors Against SRNA9 Protein Proceedings of International Conference on Drug ... Bipyrazole as Potential EGFR Kinase Inhibitors Proceedings of International Conference on Drug Discovery (ICDD) 2020 ...
CDC | TB | Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis | Recommendations | Treating Children with...
Rifampin and protease inhibitors for children with HIV and tuberculosis. There are emerging pharmacokinetic data and clinical ... Ritonavir alone should not be used as the protease inhibitor component of antiretroviral therapy in children receiving ... Therapeutic drug monitoring to evaluate efavirenz levels may be considered, if available. Additional studies are required to ... Some antiretroviral drugs are not available in liquid formulations (though increasingly, chewable and dissolvable tablets are ...
DRUG SYNTHESIS INTERNATIONAL: Amprenavir (Agenerase, GlaxoSmithKline) is a protease inhibitor.......
ALL ABOUT DRUGS, WORLD DRUG TRACKER, MEDICINAL CHEMISTRY INTERNATIONAL, DRUG SYN INTERNATIONAL SCALEUP OF DRUGS, ALL FOR DRUGS, ... ALL ABOUT DRUGS, WORLD DRUG TRACKER,MEDICINAL CHEM INTERNATIONAL, DRUG SYN INTERNATIONAL,SCALEUP OF DRUGS, ALL FOR DRUGSON WEB ... is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for ... is a protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for ...
protease inhibitor- (NS3/4A) Drug Resistance Test
File Under protease inhibitor- (NS3/4A) Drug Resistance Test, resistance to protease inhibitors ... Related;Hepatitis C-New Protease Inhibitor (NS3/4A) Drug Resistance Test 08/25/2011 09:05 am LABORATORY AMER : LabCorp ... Showing posts with label protease inhibitor- (NS3/4A) Drug Resistance Test. Show all posts ... Showing posts with label protease inhibitor- (NS3/4A) Drug Resistance Test. Show all posts ...
HIV Protease Inhibitor
Protease inhibitors are a new class of drugs that works by blocking the HIV protease. Once the protease is blocked, HIV makes ... How do protease inhibitors work?. Protease inhibitors resemble the protein chain that the protease cuts. The protease inhibitor ... Andvantages of Combination Drug Therapy. The combination of protease inhibitors and reverse transcriptase inhibitors is ... These protease inhibitors seem to be less toxic and seem to have less severe side affects than other anti-AIDS drugs ( ...
IndinavirPharmacokineticsReverse transcriptResistanceRecombinantPharmacokineticEnzymeNelfinavirDarunavirAnti-HIV drugsLopinavirAtazanavirResistance mutationsClinicalAmprenavirPharmacokineticsMutationsMetabolismEfavirenzEnzymesTherapyAffinity to the proteaseInteractionsSelectiveAntiviral ActivityNucleoside analoguesIntegrase inhibitorsAgeneraseAntiretroviral drug resistanceTargetsSerine proteasesSmall moleculeProstate-specifiInteractionRegimenReductase InhibitorsReplication20192017ConcentrationsPatientsEfficacyRitonavir-boostedProteolytic cleavageMerckInfectionMedicationsAspartyl
- We conclude that the optimal dose of indinavir in children to obtain drug exposure similar to that observed in adult patients is 50 mg/kg of MW q8h, which approximates 600 mg/m 2 q8h. (asm.org)
- We here report the pharmacokinetics of the HIV protease inhibitor indinavir in children participating in a prospective, open, uncontrolled clinical trial. (asm.org)
- The advent of triple drug therapy, which includes two nucleoside reverse transcriptase inhibitors and one protease inhibitor or two nucleoside reverse transcriptase inhibitors and one nonnucleoside reverse transcriptase inhibitor, has markedly changed therapeutic options for human immunodeficiency virus (HIV)-infected individuals. (asm.org)
- These drugs work by inhibiting the enzyme protease, which is crucial to HIV's ability to reproduce. (healthy.net)
- Protease inhibitors are compounds that block the protease enzyme of HIV, thereby preventing the production of infectious viral particles. (nih.gov)
- The discovery and definition of the importance of the HIV protease enzyme. (nih.gov)
- The definition of the structure of the HIV protease enzyme. (nih.gov)
- The development of assays to measure the inhibition of the HIV protease enzyme. (nih.gov)
- This project focuses on a viral enzyme, known as the West Nile Virus NS3 protease, that is essential for replication of the virus. (edu.au)
- By studying the enzyme in the laboratory we can design small molecules that block its function and these are potential leads for developing drug treatments for people infected, not only by this virus but potentially also other flaviviruses. (edu.au)
- The main problem is that ritonavir blocks a liver enzyme which normally destroys certain drugs, causing normal doses of the other drug to accumulate to toxic levels. (middlebury.edu)
- The proteins must be cut up by the HIV protease-a protein-cutting enzyme-to make functional new HIV particles. (poz.com)
- PIs block the protease enzyme and prevent the cell from producing new viruses. (poz.com)
- The drugs in study block the protease, an enzyme that is essential for the HIV life cycle, and in many cases are administered together with another compound that acts as a booster, allowing the drug to better metabolize in the body and work properly. (irsicaixa.es)
- Medications used in antiretroviral therapy, especially the non-nucleoside reverse transcriptase inhibitors (NNRTIs) and the protease inhibitors (PIs), are metabolized via the cytochrome P450 enzyme system (CYP450). (hivguidelines.org)
- Drugs that inhibit the CYP450 enzyme system generally lead to decreased rates of metabolism of other drugs metabolized by the same enzyme, resulting in higher drug levels and increased potential for toxicity. (hivguidelines.org)
- protease inhibitor prō´tē-ās˝ [ key ] , any of a class of drugs that interfere with replication of the AIDS virus ( HIV ), by blocking an enzyme (protease) necessary in the late stages of its reproduction. (infoplease.com)
- Clinical trials of the protease inhibitor indinavir have shown it to be especially beneficial in combination with the anti-HIV drugs AZT and 3TC, which act by blocking a different enzyme, reverse transcriptase. (infoplease.com)
- that the virus produces an enzyme or protein called protease that it must have to reproduce itself. (encyclopedia.com)
- The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: a case-control study. (medscape.com)
- Now, a new study published on the preprint server bioRxiv in August 2020 reports on the identification of 14 compounds that can inhibit the key viral enzyme called the Main Protease (MPro) at micromolar concentrations. (news-medical.net)
- An inhibitor of HIV protease, an enzyme required for production of proteins needed for viral assembly. (ebi.ac.uk)
- The mRNA is then translated into viral proteins and the third virally encoded enzyme, namely HIV protease, is required to cleave a viral polyprotein precursor into individual mature proteins. (wikipedia.org)
- The HCV protease is required for viral polyprotein processing, which makes the enzyme essential for HCV replication (Asselah and Marcellin, 2013). (prweb.com)
- These drugs prevent HIV replication by blocking the reverse transcriptase enzyme that converts RNA to DNA. (medindia.net)
- Non-nucleoside reverse transcriptase inhibitors also inhibit the reverse transcriptase enzyme. (medindia.net)
- Protease inhibitors are drugs which inhibit the protease enzyme of the HIV virus that is necessary for viral replication and infectivity. (medindia.net)
- but studies in laboratory mice have shown that nelfinavir is able to suppress the growth of tumors in these animals, which represents a promising lead towards testing this drug in humans as well. (wikipedia.org)
- Complex drug interactions of the HIV protease inhibitors 3: effect of simultaneous or staggered dosing of digoxin and ritonavir, nelfinavir, rifampin, or bupropion. (medscape.com)
- Lopinavir (LPV), nelfinavir (NEF), hydroxychloroquine (HCQ), remdesivir (RDV) and an irreversible inhibitor of SARS-CoV (N3) were used as standard drugs for COVID-19 M pro , while zafirlukast (ZFK) and cefoperazone (CSP)) as standard drugs for COVID-19 S gp . (cdc.gov)
- The effectiveness of BMS-232632 against HIV infection will be compared to that of nelfinavir, a protease inhibitor that is already commonly prescribed. (ichgcp.net)
- The European Medicines Agency has recommended updating the prescribing information for Victrelis (boceprevir) with information about drug interactions between this hepatitis C medicine and the ritonavir-boosted HIV protease inhibitors atazanavir, darunavir and lopinavir. (europa.eu)
- No drug interaction studies of darunavir and rifampin have been conducted. (cdc.gov)
- Darunavir is the first drug in a long time that didn't come with a price increase. (wikipedia.org)
- Thanks to the deep study of the virus of these 9 patients, researchers have identified mutations in the gene Gag of the virus and have shown for the first time that they are sufficient to confer resistance to darunavir , a protease inhibitor. (irsicaixa.es)
- Mitochondrial toxicity is a side effect that may be caused by the anti-HIV drugs called NRTIs . (thebody.com)
- No cross resistance with other anti-HIV drugs. (thebody.com)
- A study led by IrsiCaixa and in collaboration with the Infectious Diseases Service of the Germans Trias i Pujol Hospital discovers mutations in the Gag gene that in their own are capable of generating resistance to protease inhibitors, a family of anti-HIV drugs. (irsicaixa.es)
- Ritonavir is now approved with other anti-HIV drugs in the treatment of HIV-1 infection in children in individuals over 1 month in age. (news-medical.net)
- Taking St. John's wort with one of these anti-HIV drugs could reduce the drug's effect. (mayoclinic.org)
- Other drugs like cobicistat are used along with anti-HIV drugs to improve their effectiveness. (medindia.net)
- This drug will be given in combination with 2 other anti-HIV drugs (stavudine and didanosine). (ichgcp.net)
- The drugs saquinavir, ritonavir, and lopinavir have been found to have anti- malarial properties. (wikipedia.org)
- Lopinavir is a drug against HIV, hydroxychloroquine is used to treat malaria and rheumatism. (news-medical.net)
- Antiretroviral therapy (ART) based on the protease inhibitor lopinavir/ritonavir ( Kaletra ) does not reduce the risk of malaria among pregnant women living with HIV, research published in the online edition of the Journal of Infectious Diseases shows. (aidsmap.com)
- In this study, pregnant women were randomised to lopinavir/ritonavir vs efavirenz-based ART to test the hypothesis that a protease inhibitor based ART regimen would be associated with a lower risk of malaria," explain the authors. (aidsmap.com)
- Objective: The purpose of this article is to provide a systematic review of the pharmacokinetic and clinical data on drug-drug interactions between protease inhibitors (PIs) and statins, atazanavir and proton pump inhibitors (PPIs)and their clinical relevance. (arizona.edu)
- Results: A total of 246 references were identified, 8 of which were studies of pharmacokinetic and pharmacodynamics interactions between simvastatin, lovastatin and protease inhibitors and an additional 7 articles that provided pharmacokinetic of proton pump inhibitors and Atazanavir. (arizona.edu)
- AI424-007: Atazanavir: an HIV protease inhibitor (PI) that does not cause lipid elevations. (ichgcp.net)
- However, drug resistance mutations reduce the effectiveness of ART, and need to be monitored for effective ART. (biomedcentral.com)
- Naturally occurring primary antiretroviral drug resistance mutations have not been well analyzed in ART naïve HIV+ patients from Kenya. (biomedcentral.com)
- We examined protease inhibitor (PI) resistance mutations in ART naïve HIV-1 seropositive women from Pumwani sex worker cohort, established in Nairobi, Kenya, wherein HIV-1 infection is predominantly caused by subtypes A and D viruses. (biomedcentral.com)
- While structural understanding of the viral protease and its drug resistance mutations have been well established, the interconnectivity and development of structural cross-resistance remain unclear. (biomedcentral.com)
- The surprise was that when we studied the viruses of these patients we did not detect resistance mutations in the protease gene, which is the most classic and expected mechanism of resistance. (irsicaixa.es)
- The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. (scielo.br)
- This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil. (scielo.br)
- Data presented are medians (IQR, interquartile range) in carriers and non-carriers of only minor protease resistance mutations. (biomedcentral.com)
- ITMN-191 is a hepatitis C virus (HCV) NS3 protease inhibitor, currently in a Phase 1b clinical trial in combination with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin). (drugs.com)
- However, the Committee acknowledged that data from ongoing clinical studies in co-infected patients are needed to assess the clinical impact of these drug-interaction findings on these patients. (europa.eu)
- This paper reports the structural analyses of recent clinical mutations on the drug cross-resistance effects from various protease and protease inhibitors (PIs) complexes. (biomedcentral.com)
- Using the 2015 updated clinical HIV protease mutations, we constructed a structure-based correlation network and a minimum-spanning tree (MST) based on the following features: (i) topology of the PI-binding pocket, (ii) allosteric effects of the mutations, and (iii) protease structural stability. (biomedcentral.com)
- Our findings provide an insight into the mechanism of PI cross-resistance and may also be useful in guiding the selection of PI in clinical treatment to delay the onset of cross drug resistance. (biomedcentral.com)
- However, increasing approval of Kallikrein drugs and positive results obtained for pre-clinical treatment of HAE cases are likely to augment the growth rate of this segment moderately over the forecast period. (transparencymarketresearch.com)
- Additionally, IDX320 retained activity against mutations that produce resistance to other protease inhibitors in clinical development. (drugs.com)
- There has also been clinical trials using single and combination drug therapy. (middlebury.edu)
- There are emerging pharmacokinetic data and clinical experiences with protease-inhibitor-based antiretroviral therapy among children with HIV-related tuberculosis. (cdc.gov)
- HCV GenoSure NS3/4A represents the first in a series of HCV drug resistance assays that have been developed at Monogram Biosciences to support the clinical evaluation of HCV direct-acting antiviral (DAA) agents and their use in the management of HCV infection," commented Chris Petropoulos, PhD, LabCorp's Vice President of Monogram Research & Development. (blogspot.com)
- Recommendations recently developed by the HCV Drug Resistance Advisory Group emphasize the value of resistance testing at treatment baseline and failure in support of the development and clinical evaluation of new drug candidates. (blogspot.com)
- In HIV, the routine use of resistance testing to guide antiviral drug treatment is established in clinical practice. (blogspot.com)
- In response to the recent and future availability of DAA agents, some experts anticipate that drug resistance testing will provide similar value to the clinical management of HCV infection. (blogspot.com)
- This kind of personalized study will be key to the improvement of patient classification for clinical decisions after virological failure in order to prevent the appearance of resistant variants or favour reintroduction of protease inhibitors", says García-Prado. (irsicaixa.es)
- Saberi P, Phengrasamy T, Nguyen D. Inhaled corticosteroid use in HIV-positive individuals taking protease inhibitors: a review of pharmacokinetics, case reports and clinical management. (medscape.com)
- The U.S. Food and Drug Administration has issued draft guidance on the design, analysis, and clinical implications of drug-drug interaction studies to aid in the interpretation of future interactions [FDA (hivguidelines.org)
- Given the limited financial and clinical resources available to researchers, it is impossible to design and run randomized controlled trials to determine the effects of every possible drug-drug interaction. (hivguidelines.org)
- Several theoretical drug-drug interactions may exist given the unique nature of the pharmacokinetic and pharmacodynamic effects seen with each medication, and the clinical significance of these interactions is not always known. (hivguidelines.org)
- Clinical Drug Interaction Studies-Study Design, Data Analysis, and Clinical Implications. (hivguidelines.org)
- In preclinical studies, the Company's oral direct thrombin inhibitors have demonstrated efficacy comparable to current anticoagulants along with reduced bleeding risk and are expected to enter clinical trials in 2017. (biospace.com)
- The clinical significance of antiretroviral drug interactions is reviewed, with a focus on new and investigational agents. (mdpi.com)
- As part of the efforts to discover lead compounds for clinical use, 53 molecules were screened using molecular docking and dynamic simulations (MDS) techniques to identify potential inhibitors of SARS-CoV-2 spike protein (COVID-19 S gp ) and main protease (COVID-19 M pro ) or both. (cdc.gov)
- AI424-007: BMS-232632 - Clinical Trial AI424007: Safety, Efficacy of a Once-Daily Protease Inhibitor at 24 Weeks. (ichgcp.net)
- This type of drug has already been demonstrated to have a potent antiviral efficacy, reducing the number of viral copies in a patient during early treatment (Thompson & McHuntchison 2009) and the first protease inhibitor, boceprevir, was approved for clinical use in 2011 (FDA 2011). (scielo.br)
- However, no protease inhibitor has been presented as effective clinical drug against it. (elsevier.com)
- Moreover, the drug has a history of large-scale production and clinical use, and the issues of safety and logistics might have been cleared. (elsevier.com)
- DRUG SYNTHESIS INTERNATIONAL: Amprenavir (Agenerase, GlaxoSmithKline) is a protease inhibitor. (blogspot.com)
- Amprenavir (Agenerase, GlaxoSmithKline) is a protease inhibitor. (blogspot.com)
- Amprenavir ( Agenerase , GlaxoSmithKline ) is a protease inhibitor used to treat HIV infection. (blogspot.com)
- HIV-1 Protease dimer with Amprenavir (sticks) bound in the active site. (blogspot.com)
- Efficient and industrially applicable synthetic processes for precursors of HIV protease inhibitors (Amprenavir, Fosamprenavir) are described. (blogspot.com)
- AGENERASE (amprenavir) is an inhibitor of the human immunodeficiency virus ( HIV ) protease . (blogspot.com)
- In 2009, ten protease inhibitors have reached the market for treatment against HIV but one protease inhibitor, amprenavir, was withdrawn from the market in 2004. (wikipedia.org)
- DG17 is an orally available prodrug of DG35 (a novel HIV protease inhibitor with variable pharmacokinetics). (eurekaselect.com)
- Catherine L. Cherry, Jennifer F. Hoy, James S. Rowe, Henry Krum, John Mills and Sharon R. Lewin, " Phase 1 Single Dose Studies to Optimize the Pharmacokinetics of DG17, a Novel HIV-Protease Inhibitor Pro-Drug, Using Sodium Bicarbonate and Ritonavir", Current HIV Research (2008) 6: 272. (eurekaselect.com)
- Pharmacokinetics of recombinant secretory leukoprotease inhibitor aerosolized to normals and individuals with cystic fibrosis. (springer.com)
- As a result, there is often an incomplete correlation between predicted drug-drug interactions and in vivo pharmacokinetics. (hivguidelines.org)
- Several minor mutations were found at five different drug resistance sites. (biomedcentral.com)
- Viral compensatory secondary-line mutations mitigate this loss of fitness, equipping the virus with a broad spectrum of resistance against these drugs. (biomedcentral.com)
- Through estimation of the changes in vibrational entropies caused by each reported mutation, some secondary mutations were found to destabilize protease structure. (biomedcentral.com)
- This drug resistance arises from mutations in the viral protease gene to compromise the protease-PI interaction to facilitate the binding to protease substrate (i.e. (biomedcentral.com)
- The cross-resistance makes it challenging to map specific protease mutations to specific PIs. (biomedcentral.com)
- Mutation mappings have revealed that these mutations spontaneously arise as part of the natural variance [ 14 ] and become dominant during PI-drug treatments. (biomedcentral.com)
- Such compensatory mutations are typically found outside the protease active site or on the protease substrate Gag [ 21 - 26 ] to balance fitness with the impaired enzymatic activity. (biomedcentral.com)
- Laboratory Corporation of America® Holdings (LabCorp®) (NYSE: LH) announced today the nationwide availability of a nucleic acid sequencing assay that reports NS3 and NS4A mutations and NS3 associated resistance to the recently approved hepatitis C virus (HCV) protease inhibitors, adding to LabCorp's suite of HCV testing. (blogspot.com)
- To date 82 out of the 82 studied drug targets so far have been recorded with somatic mutations. (prnewswire.com)
- The software application lets you narrow in on these mutations and links out to the mutational analysis for each of the drug targets for detailed information. (prnewswire.com)
- To date 82 out of the 82 studied drug targets so far have been recorded with somatic mutations and the software application lets you narrow in on these mutations and links out to the mutational analysis for each of the drug targets for detailed information. (prnewswire.com)
- The number of mutations associated with nucleos(t)ide reverse transcriptase inhibitors (NRTI(t)s) did not affect virologic suppression (9.3% for zero NRTI(t)-associated mutations vs 48.6% for 1-2 NRTI(t)-associated mutations vs 42.1% for ≥3 NRTI(t)-associated mutations, p = 0.179). (springer.com)
- Drug interactions with antiretrovirals are commonly caused by the inhibition or induction of hepatic drug metabolism. (medscape.com)
- However, the high fat diet does not overcome the inhibitor going through extensive metabolism in the liver by the hepatatic cytochrome P450 3A system. (middlebury.edu)
- Inhibition of drug metabolism tends to occur quickly (based on drug half-life), with maximal effect occurring when highest concentrations of the inhibitor are reached [Hansten 1995]. (hivguidelines.org)
- Protease inhibitors can alter adipocyte metabolism causing lipodystrophy, a common side effect associated with the use of most HIV protease inhibitors. (wikipedia.org)
- Ombitasvir, paritaprevir, ritonavir fixed dose combination tablet includes a hepatitis C virus NS5A inhibitor (ombitasvir), a hepatitis C virus NS3/4A protease inhibitor (paritaprevir), and a CYP3A inhibitor (ritonavir) that inhibits CYP3A mediated metabolism of paritaprevir, thereby providing increased plasma concentration of paritaprevir. (rxlist.com)
- International Symposium on Drugs Affecting Lipid Metabolism. (ichgcp.net)
- Prediction of drug-drug Interactions Between Various Antidepressants and Efavirenz or Boosted Protease Inhibitors Using a Physiologically Based Pharmacokinetic Modelling Approach. (medscape.com)
- However, the present study showed that malaria risk and malaria-associated adverse birth outcomes were similar for women treated with the protease inhibitor and those taking the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz ( Sustiva or Stocrin ). (aidsmap.com)
- Their protease inhibitor(s) was switched to efavirenz while their NRTI therapy was maintained. (aappublications.org)
- They include drugs like efavirenz , nevirapine , delavirdine , etravirine and rilpivirine which are taken in combination with other drugs to treat HIV infections. (medindia.net)
- Efavirenz is from a class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). (aidsmap.com)
- Your doctor will prescribe efavirenz as part of your HIV treatment, along with antiretrovirals from another class of drugs. (aidsmap.com)
- Don't drink grapefruit juice with efavirenz as it can affect the level of the drug in your body. (aidsmap.com)
- Strategies to control HIV for improving the quality of patient lives have been aided by the Highly Active Anti-Retroviral Therapy (HAART), which consists of a cocktail of inhibitors targeting key viral enzymes. (biomedcentral.com)
- Numerous new drugs have been developed over the past few decades but viral resistances to these drugs in the targeted viral enzymes are increasingly reported. (biomedcentral.com)
- Further, no significant in vitro inhibition of human drug metabolizing enzymes, CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions in patients. (drugs.com)
- Once inside the cell, the virus releases its single RNA strand that codes for proteases, enzymes that cleave long viral polypeptides into functional viral-specific proteins, and polymerases that produce multiple copies of the viral RNA. (lww.com)
- Without protease, which cuts long chains of proteins and enzymes into shorter chains (which it needs to start the process), HIV cannot make copies of itself. (encyclopedia.com)
- Don't take St. John's wort if you're taking a drug affected by these enzymes. (mayoclinic.org)
- A very critical step is the proteolytic cleavage of the polypeptide precursors into mature enzymes and structural proteins catalyzed by HIV protease. (wikipedia.org)
- It works by blocking protease enzymes that are required for the virus to make DNA and replicate. (rxwiki.com)
- Potential for drug interactions should be considered when selecting antiretroviral therapy (ART) for patients with human immunodeficiency virus (HIV) infection. (medscape.com)
- Several years ago, protease inhibitors were the Great White Hope of AIDS therapy. (healthy.net)
- Currently available HIV-1 protease inhibitors are potent agents in the therapy of HIV-1 infection. (nih.gov)
- Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. (oup.com)
- Each step-viral entry, protease activity, and RNA replication-presents a potential target for drug therapy. (lww.com)
- Clearly showing that combination drug therapy is more promising than single drug therapy. (middlebury.edu)
- Ritonavir alone should not be used as the protease inhibitor component of antiretroviral therapy in children receiving tuberculosis therapy. (cdc.gov)
- Little is yet known regarding interactions between recreational drugs and ARV therapy. (hivguidelines.org)
- Herbal therapy or recreational drugs may further complicate drug interactions associated with ARV therapy because their use often goes unrecognized. (hivguidelines.org)
- An overview of known and potential interactions between medications used in the treatment of substance use, recreational drugs, and ARV therapy is presented in this chapter. (hivguidelines.org)
- Antiretroviral therapy adherence and drug-drug interactions in the aging HIV population. (medscape.com)
- Patients with HIV may be at greater risk of pharmacokinetic variability due to the nature of the infection itself or the drugs taken for antiretroviral therapy (ART). (hivguidelines.org)
- This drug may be used as part of a combination therapy. (healthline.com)
- Human immunodeficiency virus (HIV) genotypic antiretroviral drug resistance testing evaluates the likelihood that the HIV strain infecting an individual is resistant or has developed resistance to one or more antiretroviral therapy (ART) drugs. (labtestsonline.org)
- Some of these complications-hypercholesterolemia, hypertriglyceridemia, and insulin resistance-are believed to be the result of the use of protease inhibitor (PI) therapy, whereas the cause of others, such as lipodystrophy, remains undetermined. (aappublications.org)
- All patients were naïve to nonnucleoside reverse transcriptase inhibitor therapy. (aappublications.org)
- What are the Drugs Used in Antiretroviral Therapy (ART)? (medindia.net)
- 5th International Congress on Drug Therapy in HIV Infection. (ichgcp.net)
- Today's approval is the third drug for multiple myeloma approved this year and provides patients with a new oral treatment that slows disease progression when other therapy has failed," Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research, said in a press statement. (myelomacrowd.org)
Affinity to the protease2
- [ 1 , 2 ] Protease inhibitors in combination with other drugs may require dose adjustments or should be avoided because of potential drug interactions. (medscape.com)
- physicians and patients are advised to read the package label closely to assure that potentially severe drug interactions are avoided. (nih.gov)
- The package insert for fosamprenavir carries a boldfaced warning that serious and/or life-threatening drug interactions could occur between fosamprenavir and amiodarone, lidocaine (systemic), tricyclic antidepressants, and quinidine. (drugtopics.com)
- For more information on these topics, read Project Inform's publications, Lipodystrophy , Mitochondrial Toxicity and Lactic Acidosis , Bone Complications , and Drug Interactions . (thebody.com)
- No significant drug interactions. (thebody.com)
- Aptivus has many drug interactions. (thebody.com)
- Ritonavir has strong interactions with many other drugs. (middlebury.edu)
- In addition to the complexities raised by the drug interactions discussed above, treatment of pediatric HIV-related tuberculosis has additional challenges. (cdc.gov)
- Although there have been no reports of such interactions with methylergonovine alone, potent CYP 3A4 inhibitors should not be coadministered with methylergonovine. (rxlist.com)
- Chauvin B, Drouot S, Barrail-Tran A, Taburet AM. Drug-Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors. (medscape.com)
- van Heeswijk RP, Beumont M, Kauffman RS, Garg V. Review of drug interactions with telaprevir and antiretrovirals. (medscape.com)
- Wilby KJ, Greanya ED, Ford JA, Yoshida EM, Partovi N. A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients. (medscape.com)
- It includes coverage of dosage and length of time before the drug takes effect, side effects, special precautions, interactions with other food and drugs, standards for use by different age groups, and much more. (google.com)
- Clinicians should consult an experienced HIV care provider for assistance in managing drug-drug interactions between antiretroviral (ARV) agents and less common medications. (hivguidelines.org)
- Therefore, many drug-drug interactions are theoretical -based not on evidence or data, but instead on what is known about the pharmacokinetic properties of the various individual agents. (hivguidelines.org)
- There is also significant person-to-person variability in drug-drug interactions, and small sample sizes may not be adequate to identify the effects such an interaction may have on a specific patient. (hivguidelines.org)
- Therefore, when treating patients who are taking several medications for multiple comorbid conditions, expert advice may be necessary and is often recommended to ensure appropriate management of drug-drug interactions. (hivguidelines.org)
- When questions arise regarding the management of drug-drug interactions not described here, a clinician cannot assume that no interaction exists . (hivguidelines.org)
- Prescribers should become familiar with the potential for adverse effects and drug-drug interactions with all co-administered drugs they prescribe for their patients. (hivguidelines.org)
- Clinicians who manage the care of only a few patients with HIV may find it difficult to remember the potential mechanisms or effects of interactions between ARVs and other medications commonly seen in primary care settings, and drug-drug interactions may lead to symptoms attributed to ARV medications rather than the physiologic effect of an interaction. (hivguidelines.org)
- Adverse drug-drug interactions can be prevented when patients receive anticipatory guidance regarding possible interactions between prescribed medications and commonly available over-the-counter medications or supplements. (hivguidelines.org)
- Note: You can reduce your chances of drug interactions by having all of your prescriptions filled at the same pharmacy. (healthline.com)
- That way, a pharmacist can check for possible drug interactions. (healthline.com)
- Antiretrovirals are prone to drug-drug and drug-food interactions that can result in subtherapeutic or supratherapeutic concentrations. (mdpi.com)
- An overview of the mechanistic basis for drug interactions and the effect of individual antiretrovirals on CYP450 and UGT isoforms are provided. (mdpi.com)
- But because St. John's wort causes many drug interactions it might not be an appropriate choice, particularly if you take any prescription drugs. (mayoclinic.org)
- This is not a complete list of Agenerase drug interactions. (rxwiki.com)
- Potential grapefruit-drug interactions cannot be avoided by separating times of medication administration and grapefruit consumption. (aafp.org)
- Because grapefruit-drug interactions exist, strategies should be devised to manage potential interactions. (aafp.org)
- Based on drug class, the global plasma protease C1-inhibitor market is classified into C1-inhibitor, Kallikrein inhibitor, and selective Bradykinin B2 receptor antagonist (Firazyr). (transparencymarketresearch.com)
- CAMBRIDGE, Mass., April 16 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. ( NASDAQ:IDIX ) , a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today reported promising in vitro data for IDX320, an HCV protease inhibitor, demonstrating potent and selective antiviral activity in multiple genotypes, or strains, of the virus. (drugs.com)
- Characterization of selective ubiquitin and ubiquitin-like protease inhibitors using a fluorescence-based multiplex assay format. (nih.gov)
- We have demonstrated that the multiplex format is able to distinguish between selective and nonselective protease inhibitors. (nih.gov)
- Specifically, we have used this assay format to characterize P022077, a selective ubiquitin-specific protease 7 inhibitor discovered at Progenra. (nih.gov)
- However, discovery of potent and selective smallmolecule inhibitors of HCV NS3.4A protease as oral drug candidates has been hampered by the shallow substrate-binding groove of the protease. (eurekaselect.com)
- Optimization of α-ketoamide scaffolds by scientists at Vertex and Eli Lilly led to the discovery of VX-950, a novel, potent, selective inhibitor of HCV NS3.4A protease. (eurekaselect.com)
- Verseon's potent, highly selective, oral direct thrombin inhibitors act through reversible covalent inhibition, a unique mode of action. (biospace.com)
- This is called "selective pressure" because the drug "selects" and allows the proliferation of the genetic forms of the microorganism that are resistant to it. (labtestsonline.org)
- This knowledge paved the way for the development of selective inhibitors. (wikipedia.org)
- The first reports of highly selective antagonists against the HIV protease were revealed in 1987. (wikipedia.org)
- Because of the increasing prevalence of RTI- and PI-resistant HIV-1 strains, the second aim of this study was to assess the antiviral activity of APHS against drug-resistant HIV-1 strains in vitro. (rug.nl)
- Lallos, et al, "In Vitro Antiviral Activity of IDX320, a Novel and Potent Macrocyclic HCV Protease Inhibitor", Poster #768. (drugs.com)
- In order to assess whether cysteine or serine proteases promote viral spread in the host, we compared the antiviral activity of an optimized K11777-derivative with that of camostat, an inhibitor of TMPRSS2 and related serine proteases. (nih.gov)
- were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 M pro . (cdc.gov)
Antiretroviral drug resistance1
- A precedent is the success of inhibitors of HIV-1 protease that are the most effective treatment for humans with HIV-infections, and other viral proteases are now becoming recognized as viable antiviral targets for pharmaceutical development. (edu.au)
- To reduce this risk it is common to use several different drugs together that are each aimed at different targets. (wikipedia.org)
- This makes it difficult to find targets for the drug that would interfere with the virus without also harming the host organism's cells. (thefullwiki.org)
- The hepatitis C virus (HCV) NS3.4A protease, which is essential for viral replication, is considered one of the most attractive targets for developing novel anti-HCV therapies. (eurekaselect.com)
- C. Lin, A. D. Kwong and R. B. Perni, " Discovery and Development of VX-950, a Novel, Covalent, and Reversible Inhibitor of Hepatitis C Virus NS3.4A Serine Protease", Infectious Disorders - Drug Targets (2006) 6: 3. (eurekaselect.com)
- Identified drugs are linked to 408 different targets. (prnewswire.com)
- All drugs targets are further categorized on in the software application by 34 classifications of molecular function and with pathway referrals to BioCarta, KEGG, NCI-Nature and NetPath. (prnewswire.com)
- The conference will include presentations from market leaders, specialist companies and renowned experts to talk about the latest developments in COPD research, new targets in drug discovery and drug development. (smi-online.co.uk)
- Targets for nonhormonal male contraception, the pharmacologic pipeline for such targets, and the development of Epididymal Protease Inhibitor (Eppin) were the topics of a talk given by Michael G. O'Rand, PhD, Cofounder, President, and Chief Scientific Officer of Eppin Pharma, Inc, Chapel Hill, NC. (endocrineweb.com)
- Homology modeling and molecular dynamics simulations of these inhibitors in complex with their targets were carried out and, collectively, these methodologies enabled the definition of a versatile scaffold for inhibitor design. (diva-portal.org)
- Thus, the proteases have been considered as potential targets for drugs against EVD. (elsevier.com)
- A drug interaction study in healthy volunteers carried out by Merck Sharp and Dohme, the marketing authorisation holder of Victrelis, found that blood levels of all three HIV medicines were markedly lower than expected when given with Victrelis. (europa.eu)
- The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the lower blood levels seen in the drug interaction study could mean that the medicines are less effective when given together to patients who are co-infected with hepatitis C and HIV. (europa.eu)
- Doctors treating patients co-infected with hepatitis C and HIV should be aware of the findings of the drug interaction study. (europa.eu)
- Healthcare professionals in the European Union will receive a letter in the coming days to inform them of the new drug interaction data and the CHMP's recommendations while waiting for further data from ongoing studies in patients co-infected with HIV and hepatitis C. (europa.eu)
- This shows the interaction between HIV protease inhibitor and the residues that hydrogen bond to the inhibitor. (middlebury.edu)
- The combination of protease inhibitors and reverse transcriptase inhibitors is possible because there is no bad interaction between the two drugs. (middlebury.edu)
- Also known as a drug-drug interaction. (aidsmap.com)
- These alternative drugs may be substituted if a patient experiences or is at risk of a grapefruit-drug interaction. (aafp.org)
- The potential for a grapefruit-drug interaction persists for up to 72 hours according to one study. (aafp.org)
- Paritaprevir (also known as ABT-450), a potent NS3-4A serine protease inhibitor [identified by AbbVie (North Chicago, IL) and Enanta Pharmaceuticals (Watertown, MA)] of the hepatitis C virus (HCV), has been developed in combination with ombitasvir and dasabuvir in a three-direct-acting antiviral agent (DAA) oral regimen for the treatment of patients infected with HCV genotype 1. (aspetjournals.org)
- All were receiving a stable PI-containing antiretroviral regimen that containing 2 to 3 nucleoside analogue reverse transcriptase inhibitors (NRTIs) in addition to 1 to 2 PIs for a median duration of 21 months (range: 5-50) before study entry. (aappublications.org)
- Patients remain on their drug regimen for 48 weeks. (ichgcp.net)
- The three-agent combination is the first all-oral regimen for the treatment multiple myeloma, and adds to the growing roster of drug treatments for the hematologic malignancy. (myelomacrowd.org)
- NS3 serine protease inhibitors employ competitive inhibition to block the action of the NS3 serine protease and, consequently, prevent the replication of HCV (de Francesco & Carfi 2007). (scielo.br)
- For replication inside the cell, Ebola virus (EBOV) must undergo the proteolytic processing of its surface glycoprotein in the endosome by proteases including cathepsin B (CatB), followed by the fusion of the viral membrane and host endosome. (elsevier.com)
- The report forecasts the demand in the global plasma protease C1-inhibitor market will rise at a robust 20.0% CAGR for the forecast period of 2017 to 2025, for the market to be valued at US$7.9 bn by the end of 2025. (transparencymarketresearch.com)
- On the other hand, the segment of Kallikrein inhibitor (Kalbitor) is predicted to register a moderate CAGR between 2017 and 2025. (transparencymarketresearch.com)
- Bupropion in combination with either LPV/RTV or TPV/RTV will lead to decreased bupropion drug concentrations. (medscape.com)
- This raises the possibility that higher HIV-1 protease inhibitor concentrations may be obtained by targeted pharmacologic inhibition of P-glycoprotein transport activity. (nih.gov)
- Detection of SENP2core protease activity with SUMO3-GZMB and SUMO3-EK L . (A) Increasing concentrations of SENP2core (0 nM ◊, 156 pM ♦, 312 pM □, 625 pM ▪, 1.25 nM ○, 2.5 nM ∙) were incubated with 100 nM SUMO3-EK L , 20 nM of EK L substrate I. The data presented are means ± SEM of triplicate wells. (nih.gov)
- You should be aware that 1/3 patients on NVP have a rash, but only 3-5% are severe and require drug discontinuation. (thebody.com)
- You can also talk about other new drugs that are available or will soon be available by expanded access for patients who have heavy drug resistance. (thebody.com)
- Pharmacokinetic (pk) and Pharmacodynamic (pd) Results in the Phase 1b MAD Study (Poster #1861): ITMN-191 was intentionally designed to achieve a high liver-to-plasma ratio in HCV patients in order to reduce any potential side effects associated with systemic circulation of drug. (drugs.com)
- The concept and feasibility of protease inhibitors grew in part out of NIAID-supported basic research, and is an excellent example of research supported by government and industry, working together to benefit patients. (nih.gov)
- Clinicians will soon be able to offer HIV-positive patients a protease inhibitor (PI) that combines the convenience of flexible dosing with no restrictions on food or water. (drugtopics.com)
- The manufacturers urge caution when prescribing phosphodiesterase (PDE5) inhibitors for erectile dysfunction in patients taking PIs. (drugtopics.com)
- We have analyzed consensus sequences of HIV protease from 234 drug naïve patients, as a part of HIV-1 whole genome sequencing using 454 sequencing methodology. (biomedcentral.com)
- This study provides valuable data on primary drug resistance in Kenyan HIV-1 infected patients before ART became available as well as HLA mediated immune pressure over HIV-1 protease. (biomedcentral.com)
- The emergence of a few drug variants of C1-inhibitor is considered to be a major breakthrough for patients suffering from HAE that are administered either intravenously or subcutaneously. (transparencymarketresearch.com)
- The authors recommend that patients being started on these drugs first get a baseline ECG to check for prolonged QTc. (lww.com)
- Diabetes and high blood sugar (hyperglycemia) have occurred in patients taking protease inhibitors. (medicineshoppe.com)
- Some patients had diabetes before starting protease inhibitors, others did not. (medicineshoppe.com)
- Some patients with hemophilia have increased bleeding with protease inhibitors. (medicineshoppe.com)
- When the coronavirus pandemic spread across the globe, many countries resorted to using the drug in the hopes that it would improve outcomes of hospitalized patients affected by the coronavirus disease (COVID-19). (news-medical.net)
- Results from Oxford University's RECOVERY trial into existing drugs for the treatment of COVID-19 has found that dexamethasone reduced deaths by a third in ventilated coronavirus patients and by a fifth in coronavirus patients requiring oxygen. (news-medical.net)
- The British Heart Foundation is funding a trial for an experimental drug that could prevent the life-threatening blood clots that are seen in the lungs of the patients with COVID-19 or those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (news-medical.net)
- With 50-75% of patients being undiagnosed, there is a huge, global market with enormous potential for new drug treatments. (smi-online.co.uk)
- Additionally, patients with HIV are at a greater risk of the effects of polypharmacy, and the effects of multiple drugs on the pharmacokinetic pathways or pharmacodynamic effects of a single agent are not well documented. (hivguidelines.org)
- Some patients had other illnesses or were taking other drugs. (rxwiki.com)
- This can happen in patients taking tipranavir or other protease inhibitor medicines. (rxwiki.com)
- Other such drugs have recently been tested in the development phase of drug discovery and the results have been promising in the United States and Europe, mainly in untreated patients infected with genotype 1 (Kieffer et al. (scielo.br)
- The US Food and Drug Administration (FDA) today approved ixazomib ( Ninlaro , Takeda Pharmaceuticals) for the treatment of multiple myeloma patients who have received one or more previous therapies. (myelomacrowd.org)
- In addition, we suggest trials for comparison among anti-DIC drugs including the NM in EVD patients, in parallel with the experiments. (elsevier.com)
- Patients should discontinue grapefruit consumption for 72 hours before use of a drug that may interact with it. (aafp.org)
- Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving the drug chronically. (wikipedia.org)
- The Food & Drug Administration recently approved fosamprenavir (Lexiva, GlaxoSmithKline/Vertex Pharmaceuticals) for the treatment of HIV infection in adults in combination with other antiretroviral agents. (drugtopics.com)
- It is recommended that they be used in combination with at least two other HIV drugs to treat HIV infection. (poz.com)
- Employing a pathogenic animal model of SARS-CoV infection, we demonstrated that viral spread and pathogenesis of SARS-CoV is driven by serine rather than cysteine proteases and can be effectively prevented by camostat. (nih.gov)
- Thus, NM could be considered as a drug candidate for the treatment of DIC induced by EBOV infection, as well as for the possible CatB-related antiviral action. (elsevier.com)
- The clinician should conduct a thorough medication history at each visit that includes prescription medications, including those prescribed by other providers, over-the-counter medications, recreational drugs, and herbal/alternative therapies. (hivguidelines.org)
- Health care professionals should become more familiar with medications that cause irregular heart rhythms called arrhythmias, according to "Drug- Induced Arrhythmias," a new scientific statement from the American Heart Association, published today in the Association's flagship journal Circulation. (news-medical.net)
- A class of drugs refers to medications that work similarly. (healthline.com)
- They have to understand that if they do not take the medications on a regular basis, the virus can develop resistance to the drug, and make treatment more difficult. (medindia.net)
- Sildenafil is in a class of medications called phosphodiesterase (PDE) inhibitors. (medlineplus.gov)