Abstract：
:In an effort to eradicate malaria, new interventions are proposed to include compound/vaccine development against pre-erythrocytic, erythrocytic and mosquito stages of Plasmodium. Drug repurposing might be an alternative approach to new antimalarials reducing the cost and the time required for drug development. Previous in vitro studies have examined the effects of protease inhibitors on different stages of the Plasmodium parasite, although the clinical relevance of this remains unclear. In this study we tested the putative effect of three HIV protease inhibitors, two general aspartyl protease inhibitors and three AAA-p97 ATPase inhibitors on the zygote to ookinete transition of the Plasmodium parasite. Apart from the two general aspartyl inhibitors, all other compounds had a profound effect on the development of the parasites. HIVPIs inhibited zygote to ookinete conversion by 75%-90%, while the three AAA-p97 ATPase inhibitors blocked conversion by 50%-90% at similar concentrations, while electron microscopy highlighted nuclear and structural abnormalities. Our results highlight a potential of HIV protease inhibitors and p97 inhibitors as transmission blocking agents for the eradication of malaria.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
Goulielmaki E,Kaforou S,Venugopal K,Loukeris TG,Siden-Kiamos I,Koussis Kdoi
10.1016/j.molbiopara.2017.12.003subject
Has Abstractpub_date
2018-03-01 00:00:00pages
10-14eissn
0166-6851issn
1872-9428pii
S0166-6851(17)30165-2journal_volume
220pub_type
杂志文章abstract：:The promoter region of the ribosomal RNA (rRNA) genes of Leishmania amazonensis was characterised and the transcription start point, defined by primer extension, was shown to be a T residue, 1048 nucleotides upstream of the beginning of the 18S sequence. A repetitive element of 60 bp was identified in the intergenic s...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(95)02562-6
更新日期：1996-02-01 00:00:00
abstract：:Trichuris arvicolae and T. muris are gastro-intestinal nematodes of respectively arvicoline and murine rodents. We aim to investigate the ecology of these Trichuris species using population genetics. We sampled nematodes from rodents trapped in the East of France. After confirming the species identification of the nem...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2009.05.007
更新日期：2009-10-01 00:00:00
abstract：:gamma-Glutamyl transpeptidase, which is of central importance in the degradation of glutathione, was purified from Ascaris suum to apparent homogeneity. The enzyme was found to be a predominantly membrane-bound protein and was solubilized by Triton X-100. The purified enzyme, which exhibits a specific activity of 1009...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(96)02573-x
更新日期：1996-04-01 00:00:00
abstract：:The intra-species polymorphism of E. histolytica and E. dispar species in endemic area is an important tool for geographic distribution and spread mechanism studies. Since E. dispar and E. histolytica shears ecological niche, cell cycle, and transmission mechanism for human host, we studied the intra-specie variation ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2005.02.010
更新日期：2005-06-01 00:00:00
abstract：:In Trypanosoma brucei, the active variant surface glycoprotein genes (vsg) are located at telomeric expression sites (ES), whose expression is highly regulated during the life cycle. In the procyclic form, all ESs are repressed. In the bloodstream form, where antigenic variation occurs, only one of approximately 20 ES...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(98)00049-8
更新日期：1998-07-01 00:00:00
abstract：:Apicomplexan parasites utilize a peripheral membrane system called the inner membrane complex (IMC) to facilitate host cell invasion and parasite replication. We recently identified a novel family of Toxoplasma IMC Sub-compartment Proteins (ISP1/2/3) that localize to sub-domains of the IMC using a targeting mechanism ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2012.05.002
更新日期：2012-08-01 00:00:00
abstract：:The emergence of drug-resistant Leishmania species is a significant problem in several countries. A comparative proteomic analysis of antimony-susceptible and antimony-resistant Leishmania braziliensis (LbSbR) and Leishmania infantum chagasi (LcSbR) lines was carried out using two-dimensional gel electrophoresis (2-DE...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2013.06.006
更新日期：2013-08-01 00:00:00
abstract：:Adults of Onchocerca volvulus and Onchocerca gibsoni were identically fractionated into a surface-enriched fraction, a phosphate buffered saline (PBS) extract and a PBS insoluble-detergent soluble fraction. Glycoproteins were prepared from these extracts and all fractions were examined by the Western blot technique us...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(86)90102-7
更新日期：1986-09-01 00:00:00
abstract：:Cryptosporidium spp. are intracellular apicomplexan parasites that cause outbreaks of waterborne diarrheal disease worldwide. Previous studies had identified a Cryptosporidium parvum sporozoite antigen, CpMuc4, that appeared to be involved in attachment and invasion of the parasite into intestinal epithelial cells. Cp...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2014.03.005
更新日期：2014-02-01 00:00:00
abstract：:Nucleotide-sugar transporters (NSTs) transport activated sugars (e.g. UDP-GlcNAc) from the cytosol to the lumen of the endoplasmic reticulum or Golgi apparatus where they are used to make glycoproteins and glycolipids. UDP-Glc is an important component of the N-glycan-dependent quality control (QC) system for protein ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2008.01.004
更新日期：2008-05-01 00:00:00
abstract：:A myofibrillar protein extract has been isolated from the muscle of Ascaris suum. Two-dimensional electrophoresis of this extract revealed that the myosin light chain 1 (ALC1) migrates as 3 components with approximate isoelectric points in the range of 5.3-5.6. The most acidic component of ALC1 appeared to be phosphor...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(81)90007-4
更新日期：1981-06-01 00:00:00
abstract：:Representatives of all major lineages of eukaryotes contain peroxisomes with similar morphology and mode of biogenesis, indicating a monophyletic origin of the organelles within the common ancestor of all eukaryotes. Peroxisomes originated from the endoplasmic reticulum, but despite a common origin and shared morpholo...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章,评审
doi：10.1016/j.molbiopara.2016.02.005
更新日期：2016-01-01 00:00:00
abstract：:Exp-1 is an antigen of Plasmodium falciparum which is transported from the parasite cell to the membrane of the parasitophorous vacuole and to membranous compartments in the erythrocyte. To investigate how this protein is transported, we studied the synthesis and membrane translocation of exp-1 in a cell-free system. ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(91)90208-n
更新日期：1991-05-01 00:00:00
abstract：:Precipitin arcs formed after immunoelectrophoresis of Schistosoma mansoni egg, worm and cercarial antigens with polyspecific rabbit antisera have been 'stained' at neutral pH with chromogenic enzyme substrates specific for proteases and peptidases. A total of 7 antigenically distinct enzymes with peptidolytic properti...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(88)90153-3
更新日期：1988-12-01 00:00:00
abstract：:The alpha and beta tubulin genes of Leishmania major were cloned and used to study the genomic organization, chromosomal location and transcription of tubulin genes in L. major. The number of beta tubulin isogenes was determined by hybridization of probes representing the 5' and 3' ends of the cloned beta tubulin cDNA...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(87)90112-5
更新日期：1987-05-01 00:00:00
abstract：:We have previously provided evidence for a pathway in Plasmodium falciparum-infected erythrocytes, coined the parasitophorous duct pathway, which provides serum (macro)molecules direct access to intraerythrocytic parasites . The present study addresses the purity of the fluorescent macromolecules used to define the du...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(97)00039-x
更新日期：1997-07-01 00:00:00
abstract：:The usefulness of random amplified polymorphic DNA markers (RAPD) was assayed in an attempt to discriminate among species, strains and individuals within the genus Schistosoma. Depending on the species, 40-50 arbitrary decamer oligonucleotides were used as primers to amplify total DNA by the polymerase chain reaction ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(93)90219-n
更新日期：1993-06-01 00:00:00
abstract：:The synchronization of intraerythrocytic maturation of Plasmodium parasites is an important factor in the malaria infection process. Synchronization is mediated by inositol phosphate (InsP(x))-induced Ca(2+)-release from internal stores. To further investigate the InsP(x) metabolism in these parasites a Plasmodium pro...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2012.10.005
更新日期：2012-12-01 00:00:00
abstract：:The minichromosomes M210 and M230 of Leishmania major are linear amplicons which have an inverted repeat structure. We report here the molecular cloning of the megabasic chromosome region where M210 and M230 recombination points are located. The analysis of this chromosomal region revealed a 374 bp fragment directly r...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(96)02724-7
更新日期：1996-11-25 00:00:00
abstract：:The gender of cercarial larvae can only be determined using molecular methods. End point PCR methods that amplify repetitive markers on the W chromosome of the female (ZW) parasites have been developed, but sometimes results are ambiguous or incorrect. To more effectively distinguish sexes, and to determine why end po...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2016.03.010
更新日期：2016-01-01 00:00:00
abstract：:Surface and metabolic labeling procedures were used to characterize the composition and the time of expression of Brugia malayi L2 and L3 surface-associated molecules as the larvae develop within the mosquito vector. Larvae were harvested from mosquito tissues at 5 (early L2), 8 (late L2) and 11 (L3) days post-infecti...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(92)90039-m
更新日期：1992-05-01 00:00:00
abstract：:The presence of virus-derived RNA was investigated in 38 axenically growing Giardia isolates from different geographic areas. The RNA virus was demonstrated in Giardia strains from humans in the U.S.A., England and the majority of strains from Poland. Two strains isolated respectively from a cat and a cavia also conta...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(87)90190-3
更新日期：1987-02-01 00:00:00
abstract：:Some restriction fragments of kinetoplast minicircles from several trypanosomatid species (Leishmania tarentolae, Trypanosoma brucei, T. equiperdum, Herpetomonas muscarum, Crithidia fasciculata, but not T. cruzi) migrate anomalously on polyacrylamide gels. This behavior is probably due to a natural curvature of the he...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(84)90084-7
更新日期：1984-07-01 00:00:00
abstract：:Post-transcriptional regulation is a key feature controlling gene expression in the protozoan parasite Leishmania. The nine-nucleotide paraflagellar rod regulatory element (PRE) in the 3'UTR of Leishmania mexicana PFR2 is both necessary and sufficient for the observed 10-fold higher level of PFR2 mRNA in promastigotes...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2007.10.001
更新日期：2008-01-01 00:00:00
abstract：:Profilins are the key regulators of actin dynamics in all eukaryotic cells. However, little information is available on their biochemical properties and functions in kinetoplastids, such as Trypanosoma and Leishmania. We show here that Leishmania parasites express only one homolog of profilin (LdPfn), which catalyzes ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2020.111280
更新日期：2020-07-01 00:00:00
abstract：:Replication of kinetoplast DNA minicircles in Crithidia fasciculata occurs by a unidirectional mechanism involving continuous synthesis of one strand (L strand) and discontinuous synthesis of the complementary strand (H strand). L-strands are initiated by RNA priming at alternate origins (A and B) resulting in daughte...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(01)00272-9
更新日期：2001-06-01 00:00:00
abstract：:The interaction of Leishmania promastigote surface protease (PSP) with the plasmatic protease inhibitor alpha 2-macroglobulin (alpha 2M) was investigated. In plasma, solubilized PSP forms covalent complexes only with alpha 2M, at the exclusion of other protease inhibitors. The formation of complexes is accompanied by ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(89)90043-1
更新日期：1989-02-01 00:00:00
abstract：:The activity of pyrimethamine and sulfadoxine against two strains of Plasmodium falciparum has been studied in vitro by a radioisotopic technique. Low level antagonism of pyrimethamine resulted from the inclusion of p-aminobenzoic acid, p-aminobenzoylglutamic acid or folic acid in the test medium. Sulfadoxine activity...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(85)90105-7
更新日期：1985-01-01 00:00:00
abstract：:Messenger RNA has been isolated from adults and eggs of Schistosoma mansoni and translated in vitro in mRNA dependent rabbit reticulocyte lysate. The in vitro translation products have been immunoprecipitated using a wide variety of hyperimmune and infection sera from rabbits, mice and humans. A large number of in vit...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(84)90029-x
更新日期：1984-03-01 00:00:00
abstract：:Glutamate-cysteine ligase (GCL) is a heterodimer enzyme composed of a catalytic subunit (GCLC) and a modifier subunit (GCLM). This enzyme catalyses the synthesis of γ-glutamylcysteine, a precursor of glutathione. cDNAs of the putative glutamate-cysteine ligase catalytic (Ace-GCLC) and modifier subunits (Ace-GCLM) of A...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2014.07.003
更新日期：2014-08-01 00:00:00
