Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As dendritic antigen-presenting cells in skin and mucous membranes, Langerhans cells (LC) are found in areas at risk of inoculation by the human immunodeficiency virus (HIV). LC have been reported as targets for HIV-1. The aim of the present study was to investigate whether LC can be experimentally infected by HIV provided by a cell-free infection system. A cell-free suspensions was prepared from viral particles provided by chronically infected cell lines (U937 or H9 cells) by low-speed centrifugation followed by 0.45-microns filtration. LC-enriched epidermal cell (EC) suspensions with no CD3+ cells (assessed by flow cytometry and electron microscopy) and uninfected U937 cells (cell-free infection system control) were infected with two isolates (HTL VIII-B and RF). The infectiousness of the cell-free virus fluids was controlled on U937 cells where proviral DNA was amplified (gag, pol, and env gene sequences by the polymerase chain reaction, PCR) and release of virus particles into the supernatant was controlled either by measure of the reverse transcriptase (RT) activity or detection of viral RNA amplified by RT-PCR for the gag gene sequences). Proviral DNA (gag gene sequences) was found in LC-enriched epidermal cellular DNA from day 4 post-infection with isolate HTL VIII-B and from day 7 with isolate RF. Although the RT activity did not reach a significantly high level, viral RNA was found in the supernatant of LC-enriched EC cultures at the same time as proviral DNA was detected in LC.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Detection of HIV-specific DNA sequences in epidermal Langerhans cells infected in vitro by means of a cell-free system. 772 34

Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free assays using purified recombinant HIV RT as well as for their anti-HIV activity in HTL VIIIB-infected peripheral blood mononuclear cells. Our computational approach allowed the identification of several ligand derivatization sites for the generation of more potent S-DABO derivatives. Our lead S-DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one (compound 3), elicited potent anti-HIV activity with an IC50 value of less than 1nM for inhibition of HIV replication without any evidence of cytotoxicity and an unprecedented selectivity index of > 100,000.
 ...
PMID:5-Alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series. 987 70