Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fundamental role played by reverse transcriptase (RT) in the replication of retroviruses has made this enzyme a key target in the chemotherapy of HIV infection. Since the replicative cycle of HIV is interrupted by RT inhibitors, the inhibition of HIV RT is currently considered as a useful approach in the prophylaxis and intervention of AIDS. The MeOH and water extracts of 41 medicinal plants used in Egyptian folk medicine were evaluated for their HIV-1 RT inhibitory effects, and inhibitory substances were identified from the fruit of Phyllanthus emblica that showed a potent inhibitory activity to HIV-1-RT. The enzyme activity was determined by the amount of tritium labeled-substrate incorporation into a polymer fraction in the presence of a template-primer. Of the plant materials tested, the fruits of Phyllanthus emblica L. (MeOH extract), Quercus pedunculata (MeOH and water extracts), Rumex cyprius (MeOH and water extracts), Terminalia bellerica (MeOH and water extracts), Terminalia chebula (MeOH and water extracts), and Terminalia horrida (MeOH extract) showed significant inhibitory activity with IC50 of 2-49 mcg/ml. However, in the presence of bovine serum albumin (BSA), the inhibitory potency of most of the extracts, except for P. emblica (MeOH extract) and T. chebula (water extract), was appreciably reduced by nonspecific binding of their ingredients with BSA. Through a bioassay guided-fractionation of the methanol extract of the fruit of P. emblica, putranjivain A (1) was isolated as a potent inhibitory substance with IC50 = 3.9 mcM, together with 1,6-di-O-galloyl-beta-D-glucose (2), 1-O-galloyl-beta-D-glucose (3), kaempferol-3-O-beta-D-glucoside (4), quercetin-3-O-beta-D-glucoside (5), and digallic acid (6). The inhibitory mode of action by 1, 2, and 6 was noncompetitive with respect to the substrate but competitive with respect to a template-primer. Furthermore, the stereochemistry of 1 was established in this paper by nuclear magnetic resonance spectroscopy.
 ...
PMID:Inhibitory effects of Egyptian folk medicines on human immunodeficiency virus (HIV) reverse transcriptase. 754 17

Noma (cancrum oris) is a severe gangrene of the soft and hard tissues of the mouth, face, and neighboring areas observed especially in children. Without the timely intervention of appropriate antibiotics, noma is almost always quickly fatal. Survivors of the disease may exhibit facial mutilation, impaired growth of the facial skeleton, nasal regurgitation of food, leakage of saliva, defective speech, and chewing difficulties. Noma is frequently seen in developing countries, especially in sub-Saharan Africa, where it occurs almost exclusively among poor children usually aged 3-10 years. It may be that noma results from oral contamination by a heavy load of Bacteroidaceae and a consortium of other microorganisms. The opportunistic pathogens invade oral tissues when an individual's immune response is compromised by malnutrition, acute necrotizing, gingivitis, debilitating conditions, trauma, and other oral mucosal ulcers. Accordingly, malnutrition, poor oral hygiene, and debilitation resulting from HIV infection, measles, and other childhood diseases prevalent in the tropics are factors associated with an increased probability of developing noma. Poverty, however, is the most important risk indicator for the condition. The current escalation in the incidence of noma in Africa can be attributed to the worsening economic crisis in the region. The prevention of noma in Africa will require measures which address these problems and, most importantly, eliminate the fecal contamination of food and water supplies.
 ...
PMID:Noma: a neglected scourge of children in sub-Saharan Africa. 755 28

In an attempt to determine whether immunization of healthy HIV-1 seronegative individuals with a soluble gp160 candidate vaccine could induce an anti-HIV specific immune response, volunteers were immunized by two injections of a water-in-oil emulsion containing a mixture of gp160 antigen together with selected peptides. Following immunization, lymphocytes were collected and stimulated in vitro with autologous HIV-1-infected cells. The results showed that immunization with soluble HIV-1 envelope was able to generate CD3+ CD8+ CTLs directed to gp160 antigen. The CTL response was restricted to class I molecule HLA-A2. The CTL response was comparable to that elicited by immunization with HIV-1-envelope recombinant vaccinia virus.
 ...
PMID:HIV-1 soluble antigens induced CD8+ cytotoxic T-cell responses in an immunized individual. 758 Aug 33

Environmental survival of human immunodeficiency virus type 1 (HIV-1) is an important public health concern. Survival of HIV in waste water is of particular interest to those who work at treatment facilities and to the general public who have contact with rivers or ocean water receiving treated sewage effluent. Other researchers have reported that HIV can be detected in waste water. Their studies, however, detected homologous nucleic acid sequences but did not attempt to determine infectivity. The current study tested primary and secondary effluent from a major metropolitan sewage agency for the presence of HIV-1 using reverse transcriptase polymerase chain reaction (RT-PCR), HIV-1 p24 antigen enzyme-linked immunosorbent assay, and infectivity testing. For RT-PCR, primers SK38/SK39 and M667/AA55 were used to identify HIV-1 RNA sequences from concentrated and extracted sewage samples. Infectivity assays employed donor peripheral blood mononuclear cells (PBMCs) stimulated with phytohemagglutinin. Coxsackievirus B4, echovirus 7, and poliovirus 1, enteroviruses normally present in sewage, were tested for replication in PBMCs. Poliovirus 1 was found to infect the PBMCs. To eliminate other enteroviruses that may also infect the PBMCs and interfere with HIV-1 testing, concentrated sewage was treated with human immunoglobulin (free of HIV antibodies) and poliovirus antisera before infectivity assays were performed. All treated sewage samples tested negative for HIV-1 by all methods used. HIV-1 seeded into sewage, however, remained infectious in the assay, indicating that the sewage water sample did not interfere with HIV infectivity nor was it toxic to the PBMCs.
 ...
PMID:Analysis of sewage effluent for human immunodeficiency virus (HIV) using infectivity assay and reverse transcriptase polymerase chain reaction. 758 58

The disulfide bridge closed cyclic peptide corresponding to the whole Consensus V3 loop of the envelope protein gp120 of HIV-1 was examined by proton 2D-NMR spectroscopy in water and in a 20% trifluoroethanol/water solution. In water, NOE data support a beta-turn conformation for the central conservative GPGR region and point towards partial formation of a helix in the C-terminal part. Upon addition of trifluoroethanol, a C-terminal helix is formed. This is evidenced by NOE data, alpha-proton chemical shift changes and changes in the JN alpha vicinal coupling constants. The C-terminal helix is amphipathic and also occurs in other examined strains. It could therefore be an important feature for the functioning of the V3 loop.
 ...
PMID:The complete Consensus V3 loop peptide of the envelope protein gp120 of HIV-1 shows pronounced helical character in solution. 758 96

NMR spectroscopy has been used to solve the three-dimensional solution structure of a minimal RNA-binding domain of the Rev protein from the human immunodeficiency virus (type 1), an essential regulatory protein for viral replication. The presence of 10 arginine residues in the 17-residue peptide Rev34-50 caused significant problems in assignment of the NMR spectra. To improve spectral resolution, the peptide was synthesized with an alanine replacing a nonessential arginine and with selectively 15N-labeled residues. Contrary to Chou-Fasman modeling predictions an alpha-helix was detected in both water and 20% trifluoroethanol (TFE) and was found to span residues that constitute the RNA-binding and nuclear-localizing domains of Rev. The sequence-specific information provided by the NMR data gives a full description of the solution conformation of Rev34-50 which serves as a template for investigating binding of the peptide to RNA from the Rev response element (RRE). Preliminary modeling suggests that the helix can fit neatly into the expanded major groove of the RRE where interactions between the peptide side chains and the RNA can be identified. These data may aid the construction of a suitable pharmacophore model for the rational design of molecules that block Rev-RNA binding and inhibit HIV replication.
 ...
PMID:NMR solution structure of the RNA-binding peptide from human immunodeficiency virus (type 1) Rev. 759 17

SPC3 is a synthetic multibranched peptide containing eight HIV-1 gp120 V3 loop GPGRAF motifs. SPC3 inhibits HIV-1 infection in human lymphocytes and macrophages, while the monomer counterpart of SPC3, i.e., the GPGRAF peptide, has no effect. Circular dichroism (CD) of these molecules in phosphate buffer, pH 7, and in a water solution containing 50% trifluoroethanol (TFE) showed significant differences. In TFE, the inactive monomer has a CD spectrum associated to type II beta-turn (class B spectrum), while SPC3 has a class C CD spectrum associated to type I beta-turn. To investigate the structure--function relationship, SPC3 analogs were built in solid-phase synthesis, and their activity and structures were compared to SPC3. Analogs having respectively two and four GPGRAF motifs show that polymerization is associated with these structural changes. Analogs with eight motifs but differing in their sequence show also that the sequence is important to stabilize a type I beta-turn structure. The activity tests of these analogs show a remarkable correlation between the antiviral activity and their ability to exhibit a class C CD spectrum associated to type I beta-turn. Taking in account CD results, a model was made using energy minimization and dynamics, which shows that, for SPC3, a model with motifs in a type I beta-turn structure is favored compared to one with a type II beta-turn. These data suggest that the SPC3 antiviral activity is related to the structure of the GPGRAF motif in the polymer, with special emphasis on the presence of a type I beta-turn structure.
 ...
PMID:Correlation of antiviral activity with beta-turn types for V3 synthetic multibranched peptides from HIV-1 gp120. 759 21

Rotavirus, which is the most common cause of infantile diarrhea worldwide, mainly affects infants between the ages of 6 and 24 months. Most infections in human newborns are mild or asymptomatic, due to the inherently attenuated nature of the "nursery" rotavirus strains. Adults are also sometimes affected, especially those in families with an infected child; the disease also occurs in closed adult communities. HIV-infected persons, travelers, or as a result of water-borne epidemics. Nosocomially acquired hospital infections add to morbidity and to the cost of hospitalization. A winter predominance of rotavirus diarrhea has been noted in temperate climates but not in tropical areas. Group A rotavirus infections are generally more common, but human infections with groups B and C have also been documented. The prevalence of serum antibodies is high during the neonatal period, but it declines sharply between the ages of 3 and 6 months, then rises steeply, peaking at approximately 2 years and remaining high into adulthood. Vaccines against rotavirus are currently under evaluation.
 ...
PMID:The epidemiology of rotavirus infections: a global perspective. 760 22

The lack of a safe, economical murine lentivirus model for human immunodeficiency virus type 1 (HIV-1) infection of humans has hampered the preclinical evaluation of potential antiviral compounds, vaccines, and biological response modifiers. A small animal model that does not employ HIV-1 is needed to minimize risk of accidental human exposure, enhance efficient use of scarce experimental compounds, and reduce laboratory space necessary to conduct statistically significant in vivo trials. Feline immunodeficiency virus (FIV), an immunosuppressive lentivirus of domestic cats, has been used extensively as an animal model for the pathogenesis and therapy of human HIV-1 infection. Cats, however, are not amenable to large-scale efficacy trials because of their relatively large size, high cost, and limited degree of physiologic characterization, particularly with regard to drug metabolism. To adapt the feline immune system to a small laboratory animal host, severe combined immunodeficient mice (SCID mice) were engrafted with feline lymphoid tissues (forming the SCID-fe mouse) and inoculated with FIV. Two quantitative parameters, the incidence of provirus detection in feline tissue grafts and the level of feline IgG in plasma, were used to demonstrate the antiviral efficacy of 3'-azido-3'-deoxythymidine (AZT, azidothymidine, Retrovir, zidovudine) in the SCID-fe system. Of 17 SCID-fe mice inoculated with 7 x 10(6) peripheral blood mononuclear cells (PBMC) from an FIV-infected cat, eight had detectable FIV provirus in both the feline thymus and feline lymph node implants, as measured by polymerase chain reaction (PCR)/Southern blot analysis. Treatment of these mice with AZT at a dose of 125 mg kg-1 day-1 in drinking water beginning 1 day prior to FIV inoculation and continuing throughout the study interval prevented the dual detection of provirus in feline lymph node and thymus grafts of all mice tested. In a separate experiment, the level of spontaneous feline IgG production was quantified by ELISA 2 weeks after FIV inoculation with and without AZT treatment. Mean plasma feline IgG level of five SCID-fe mice inoculated with 10(3) TCID50 cell-free FIV was 2.23 mg ml-1. Mean feline IgG level of five mice inoculated with the same quantity of FIV and treated with AZT beginning 1 day prior to virus inoculation and continuing for 2 weeks thereafter was 14.98 mg ml-1. AZT significantly (P < 0.05) enhanced feline humoral immune function at a virus inoculum titer of 10(3) TCID50.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Reduced provirus burden and enhanced humoral immune function in AZT-treated SCID-feline mice inoculated with feline immunodeficiency virus. 761 56

3'-Azido-3'-deoxythymidine (AZT), the main antiretroviral drug used against Human Immunodeficiency Virus, was approved by the Food and Drug Administration in 1987 with only little knowledge concerning its metabolism. The aim of our study was to evaluate the interspecies variability of AZT metabolism in primary cultures of hepatocytes, freshly isolated from rats, dogs, monkeys, and humans. Cultures were exposed to 10 or 100 microM [3H]AZT. Extracellular and intracellular compartments were analyzed using a HPLC method. Intracellular and extracellular metabolic patterns were qualitatively similar, but very low amounts of AZT and metabolites were detected within hepatocytes. In all species, the 3'-azido-3'-deoxy-5'-O-beta-D-glucopyranuronosylthymidine (GAZT) was identified as the major metabolite of AZT. In addition to this glucuronide, two minor peaks were detected: one coeluting with 3'-amino-3'-deoxythymidine(AMT); and the other with a retention time corresponding, on the basis of the publications in this field, to 3'-amino-3'-deoxythymidine glucuronide. However, further investigation allowed this compound to be characterized as tritiated water, possibly representing a catabolic endproduct of AZT. Although glucuronidation was the main metabolic pathway in the four species studied, AZT biotransformation rate was much lower in rat and dog hepatocytes than in monkey and human ones. Finally, an excellent correlation was obtained between in vivo and in vitro metabolic data.
 ...
PMID:Comparative metabolism of 3'-azido-3'-deoxythymidine in cultured hepatocytes from rats, dogs, monkeys, and humans. 762 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>